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Objective: To investigate the association between antidepressant use in late gestation and postpartum haemorrhage (PPH).Design: Retrospective cohort study.Setting: Tertiary teaching hospital in Adelaide, Australia.Population: A total of 30 198 women delivering between 2002 and 2008.Methods: Relative risks adjusted for maternal sociodemographics and comorbidities (aRRs) were calculated for PPH, comparing women with late-gestation exposure to antidepressants (n = 558), women with a psychiatric illness but no antidepressant use (n = 1292), and women with neither antenatal exposures (n = 28 348). Additional sensitivity analyses were undertaken, examining associations with severe PPH and postpartum anaemia.Main Outcome Measures: The primary outcome was PPH, defined as a recorded blood loss of ≥500 mL for vaginal deliveries and ≥1000 mL for caesarean sections. Secondary outcomes included severe PPH (≥1000 mL blood loss, irrespective of method of delivery), and the presence of postpartum anaemia (identified from hospital medical records).Results: Compared with unexposed controls, women exposed to antidepressants had an increased risk of PPH (aRR 1.53; 95% confidence interval, 95% CI 1.25-1.86), whereas no increased risk was observed for women with a psychiatric illness but no antidepressant use (aRR 1.04; 95% CI 0.89-1.23). In sensitivity analyses, late gestation antidepressant exposure was associated with an increased risk of severe PPH (aRR 1.84; 95% CI 1.39-2.44), as well as postpartum anaemia (aRR 1.80; 95% CI 1.46-2.22).Conclusions: Exposure to antidepressants in late gestation was associated with a significantly increased risk of PPH. Although potential confounding by unmeasured factors cannot be ruled out, these findings suggest a direct effect of antidepressant exposure on PPH.Tweetable Abstract: Late gestation antidepressant exposure is associated with a significantly increased risk of postpartum haemorrhage. [ABSTRACT FROM AUTHOR]

RATIONALE: Inhaled corticosteroids (ICS) are currently advised for the control of asthma during pregnancy, despite the lack of evidence regarding potential systemic effects on maternal, placental, and fetal systems. OBJECTIVES: To determine maternal plasma concentrations of cortisol, estriol, osteocalcin, and corticotropin-releasing hormone in pregnant women with asthma (n = 156) and without asthma (n = 51). METHODS: During each trimester of pregnancy, the use and dose of ICS was recorded and blood samples were collected. Ultrasound was performed at 18 and 30 weeks' gestation, and birth weight and fetal sex were recorded at delivery. MEASUREMENTS AND MAIN RESULTS: Maternal hormone concentrations were not affected by the presence of asthma; however, they were inhibited by ICS use in a dose-dependent manner. This was dependent on fetal sex: in pregnancies with a female, ICS was inversely associated with maternal cortisol in first trimester and inversely associated with maternal osteocalcin in second and third trimester. When pregnant with a male, no effect of ICS dose was observed on maternal cortisol, estriol, or osteocalcin levels, whereas corticotropin-releasing hormone levels were increased with ICS use only in the first trimester. CONCLUSIONS: Maternal glucocorticoid-regulated systems appeared susceptible to ICS only when pregnant with a female. Fetal adrenal function appeared unaffected by ICS in pregnancies of both males and females. This provides clinically important information suggesting that ICS do not exert effects on glucocorticoid-regulated pathways in the fetus, and therefore are unlikely to contribute to adverse effects on fetal growth and development. [ABSTRACT FROM AUTHOR]

Asthma during pregnancy is associated with a low birth weight, although the mechanisms contributing to this outcome remain unknown. The relationship between maternal asthma and its treatment, placental function, fetal sex, and low birth weight was examined to establish the effect of asthma on fetal growth. Glucocorticoid intake by women with asthma was assessed throughout pregnancy. The placenta was collected after delivery, and 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity was measured. Fetal cortisol and estriol were measured in the umbilical vein plasma at delivery. Those with asthma were compared with a nonasthmatic control group. In women with asthma who did not use inhaled steroids and were pregnant with a female fetus, we observed significantly reduced birth weights, whereas male birth weights were unaffected. The presence of a female fetus was associated with significantly increased maternal circulating monocytes, significantly reduced placental 11beta-HSD2 activity and fetal estriol, and a trend toward elevated fetal plasma cortisol. This study provides evidence that in pregnancies complicated by asthma there is a fetal sex-specific effect on the maternal immune system with adverse effects on placental function and female fetal growth. [ABSTRACT FROM AUTHOR]

Objectives: To characterise the relationships between peripheral microvascular blood flow and measures of physiological and cardiovascular function in preterm infants in the immediate newborn period. Design: Prospective observational cohort study. Setting: Tertiary neonatal intensive care unit, New South Wales, Australia. Patients: Ninety-six preterm neonates (24-36 weeks' gestation) admitted to the neonatal intensive care unit. Main Outcome Measure: Relationship between laser Doppler-derived basal microvascular blood flow, functional echocardiographic measurements of cardiovascular status, mean arterial blood pressure and clinical illness severity at 24, 72 and 120 h of age. Results: At 24 h of age, multiple linear regression revealed a significant positive relationship, independent of gestational age, between baseline microvascular blood flow and clinical risk index for babies (CRIB II) score (r2 = 0.442). Microvascular blood flow was inversely related to mean arterial blood pressure (r2 = -0.563), and correlated positively with left ventricular output (r2 = 0.435). Microvascular blood flow continued to exhibit a significant inverse relationship with mean arterial blood pressure (r2 = -0.4) at 72 h of age, but by 120 h no significant relationships were evident. Conclusions: This is the first study to show that baseline microvascular blood flow in premature infants exhibits significant relationships with clinical illness severity and cardiovascular function in the immediate postnatal period. The effects of temporal and functional changes in the microvasculature on cardiovascular adaptation warrant further detailed study. [ABSTRACT FROM AUTHOR]

Maternal asthma is associated with increased rates of neonatal lung disease, and fetuses from asthmatic ewes have fewer surfactant-producing cells and lower surfactant-protein B gene (SFTPB) expression than controls. Antenatal betamethasone increases lung surfactant production in preterm babies, and we therefore tested this therapy in experimental maternal asthma. Ewes were sensitised to house dust mite allergen, and an asthmatic phenotype induced by fortnightly allergen lung challenges; controls received saline. Pregnant asthmatic ewes were randomised to receive antenatal saline (asthma) or 12 mg intramuscular betamethasone (asthma+beta) at 138 and 139 days of gestation (term = 150 days). Lambs were delivered by Caesarean section at 140 days of gestation and ventilated for 45 min before tissue collection. Lung function and structure were similar in control lambs (n = 16, 11 ewes) and lambs from asthma ewes (n = 14, 9 ewes). Dynamic lung compliance was higher in lambs from asthma+beta ewes (n = 12, 8 ewes) compared to those from controls (P = 0.003) or asthma ewes (P = 0.008). Lung expression of surfactant protein genes SFTPA (P = 0.048) and SFTPB (P < 0.001), but not SFTPC (P = 0.177) or SFTPD (P = 0.285), was higher in lambs from asthma+beta than those from asthma ewes. Female lambs had higher tidal volume (P = 0.007), dynamic lung compliance (P < 0.001), and SFTPA (P = 0.037) and SFTPB gene expression (P = 0.030) than males. These data suggest that betamethasone stimulates lung maturation and function of near-term neonates, even in the absence of impairment by maternal asthma., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)

Objective: Maternal obesity (MO) increases the risk of later-life liver disease in offspring, especially in males. This may be due to impaired cytochrome P450 (CYP) enzyme activity driven by an altered maternal-fetal hormonal milieu. MO increases fetal cortisol concentrations that may increase CYP activity; however, glucocorticoid receptor (GR)-mediated signaling can be modulated by alternative GR isoform expression. We hypothesized that MO induces sex-specific changes in GR isoform expression and localization that contribute to reduced hepatic CYP activity., Methods: Nonpregnant, nulliparous female baboons were assigned to either an ad libitum control diet or a high-fat, high-energy diet (HF-HED) at 9 months pre pregnancy. At 165 days' gestation (term = 180 days), fetal liver samples were collected (n = 6/sex/group). CYP activity was quantified using functional assays, and GR was measured using quantitative RT-PCR and Western blot., Results: CYP3A activity was reduced in the HF-HED group, whereas CYP2B6 activity was reduced in HF-HED males only. Total GR expression was increased in the HF-HED group. Relative nuclear expression of the antagonistic GR isoform GRβ was increased in HF-HED males only., Conclusions: Reduced CYP activity in HF-HED males may be driven in part by dampened hepatic-specific glucocorticoid signaling via altered GR isoform expression. These findings highlight targetable mechanisms that may reduce later-life sex-specific disease risk., (© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Group B Streptococcus (GBS) asymptomatically colonises the vagina of up to 40% of pregnant women and can transmit to neonates during birth, causing neonatal pneumonia, sepsis, meningitis, and significant mortality. Vaginal GBS colonisation can be attributed to a range of host and bacterial factors, which may include the composition of the vaginal microbial community. There are few studies that have examined the vaginal community composition in relation to GBS colonisation throughout pregnancy. Here, we performed 16S rRNA sequencing (V3-V4) on vaginal swabs from women at 24- and 36-weeks' gestation, who were GBS culture-negative or GBS culture-positive at either 24 weeks or 36 weeks' gestation or at both timepoints. Vaginal swabs from 93 women were analysed; 46 women were culture-negative, 11 women GBS culture-positive at 24 weeks only, 21 women GBS culture-positive at 36 weeks only and 15 women GBS culture-positive at both timepoints on Brilliance GBS agar. V3-V4 16S rRNA gene amplicon sequencing demonstrated that in women that were GBS culture-positive at 36 weeks gestation only, G. vaginalis was significantly more abundant at 24-weeks' gestation despite a lack of significant changes in community richness between the 24- and 36-week samples. The vaginal microbial communities of women persistently colonised with GBS, had a significantly higher abundance of Lactobacillus iners , compared to other groups where L. crispatus, L. gasseri or L. jensenii were dominant. We have characterised the vaginal microbial community composition during pregnancy in relation to GBS colonisation status, in a longitudinal study for the first time. The most interesting finding was that in women that were persistently colonised with GBS throughout pregnancy, there was a significant increase in L. iners and significant reduction in L. crispatus abundance. Given the lack of detail of the role that the vaginal microbial community plays in GBS colonisation in the literature, it is imperative that the relationship between L. iners and GBS in this unique environmental niche is further investigated., Competing Interests: Author JB was employed by Mater Misericordiae Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Maidment, Pelzer, Borg, Cheung, Begun, Nitert, Rae, Clifton and Carey.)

Maternal asthma affects up to 17% of pregnancies and is associated with adverse infant, childhood, and adult respiratory outcomes, including increased risks of neonatal respiratory distress syndrome, childhood wheeze and asthma. In addition to genetics, these poor outcomes are likely due to the mediating influence of maternal asthma on the in-utero environment, altering fetal lung and immune development and predisposing the offspring to later lung disease. Maternal asthma may impair glucocorticoid signalling in the fetus, a process critical for lung maturation, and increase fetal exposure to proinflammatory cytokines. Therefore, interventions to control maternal asthma, increase glucocorticoid signalling in the fetal lung, or Vitamin A, C, and D supplementation to improve alveologenesis and surfactant production may be beneficial for later lung function. This review highlights potential mechanisms underlying maternal asthma and offspring respiratory morbidities and describes how pregnancy interventions can promote optimal fetal lung development in babies of asthmatic mothers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background/Objectives : The utility of shear wave elastography (SWE) as an adjunct to ultrasound biometry and Doppler velocimetry for the examination of placental dysfunction and suboptimal fetal growth is unclear. To date, limited data exist correlating the mechanical properties of placentae with fetal growth. This study aimed to investigate the relationship between placental shear wave velocity (SWV) and ultrasound estimated fetal weight (EFW), and to ascertain if placental SWV is a suitable proxy measure of placental function in the surveillance of small-for-gestational-age (SGA) pregnancies. Methods : This prospective, observational cohort study compared the difference in placental SWV between SGA and appropriate-for-gestational-age (AGA) pregnancies. There were 221 women with singleton pregnancies in the study cohort-136 (61.5%) AGA and 85 (38.5%) SGA. Fetal biometry, Doppler velocimetry, the deepest vertical pocket of amniotic fluid, and mean SWV were measured at 2-4-weekly intervals from recruitment to birth. Results : There was no difference in mean placental SWV in SGA pregnancies compared to AGA pregnancies, nor was there any relationship to EFW. Conclusions : Although other studies have shown some correlation between increased placental stiffness and SGA pregnancies, our investigation did not support this. The mechanical properties of placental tissue in SGA pregnancies do not result in placental SWVs that are apparently different from those of AGA controls. As this study did not differentiate between constitutionally or pathologically small fetuses, further studies in growth-restricted cohorts would be of benefit.

Glucocorticoids exert pleiotropic effects on all tissues to regulate cellular and metabolic homeostasis. Synthetic forms are used therapeutically in a wide range of conditions for their anti-inflammatory benefits, at the cost of dose and duration-dependent side effects. Significant variability occurs between tissues, disease states, and individuals with regard to both the beneficial and deleterious effects. The glucocorticoid receptor (GR) is the site of action for these hormones and a vast body of work has been conducted understanding its function. Traditionally, it was thought that the anti-inflammatory benefits of glucocorticoids were mediated by transrepression of pro-inflammatory transcription factors, while the adverse metabolic effects resulted from direct transactivation. This canonical understanding of the GR function has been brought into question over the past 2 decades with advances in the resolution of scientific techniques, and the discovery of multiple isoforms of the receptor present in most tissues. Here we review the structure and function of the GR, the nature of the receptor isoforms, and the contribution of the receptor to glucocorticoid sensitivity, or resistance in health and disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Clinical and preclinical evidence indicate that in utero maternal asthma exposure increases progeny asthma risk. Whether maternal asthma also increases the risks of progeny allergy is unclear., Objectives: To synthesise the available evidence on the relationship between in utero exposure to maternal asthma and postnatal asthma, wheezing and allergic diseases (Prospero: CRD42020201538)., Search Strategy: We systematically searched MEDLINE [PubMed], Embase [Ovid], Web of Science, Informit Health, the Cochrane Library, CINAHL [EBSCOhost], MedNar [Deep Web Technologies], ProQuest Theses and Dissertations, Scopus [Elsevier] and Trove, to the end of 2023., Selection Criteria: Studies reporting asthma, wheeze and/or allergic disease in progeny of women with and without asthma or with asthma classified by control, exacerbation or severity., Data Collection and Analysis: Double screening, selection, data extraction and quality assessment were performed, using Joanna Briggs Institute (JBI) scoring., Main Results: Of 134 non-overlapping studies, 127 were included in ≥1 meta-analysis. Maternal asthma ever was associated with greater risks of asthma (65 studies, risk ratio [95% confidence interval] 1.76 [1.57-1.96]), wheeze (35 studies, 1.59 [1.52-1.66]), food allergy (5 studies, 1.32 [1.23-1.40]), allergic rhinitis (7 studies, 1.18 [1.06-1.31]) and allergic dermatitis (14 studies, 1.17 [1.11-1.23]) ever in progeny. Asthma during the pregnancy, more severe, and uncontrolled maternal asthma were each associated with greater risks of progeny asthma., Conclusions: Children of mothers with asthma are at increased risk for the development of allergic diseases. Whether improved maternal asthma control reduces risks of child allergy as well as asthma requires further investigation., (© 2024 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objectives: Antenatal exercise is associated with placental morphological alterations, however research in this area is limited. Given the emphasis on the beneficial effects of antenatal exercise, it is important to understand its effect on placental function and the relationship to foetal development. The aim of this study was to investigate the association between physical activity, sitting time, and placental outcomes measured during gestation., Design: Prospective cohort study., Methods: Pregnant women in the Queensland Family Cohort study self-reported physical activity at 24 and 36 weeks of gestation (n = 203) and were categorised into physical activity volume groups of nil-low (0-<500 metabolic equivalent of task·minutes/week), moderate (500-<1000 metabolic equivalent of task·minutes/week), or high-volume activity (≥1000 metabolic equivalent of task·minutes/week). Participants reported average daily sitting time, whereby excessive sitting time was considered as ≥8h/day. Placental stiffness, thickness, and uteroplacental blood flow resistance were measured by ultrasound imaging at each timepoint., Results: Physical activity volume was not associated with changes to placental morphometrics or uteroplacental blood flow resistance at 24 or 36 weeks of gestation. Excessive sitting time at 36 weeks was associated with greater placental stiffness (p = 0.046), and a lower umbilical artery pulsatility index (p = 0.001)., Conclusions: Placental tissue stiffness and umbilical artery resistance were altered in late gestation with higher maternal sitting time but not with physical activity volume. Overall, excessive sitting time may be a risk for suboptimal placental function and could be an important focus for antenatal care., Competing Interests: Declaration of interest statement The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background. Previous research has shown that delivery mode can shape infant gut microbiome composition. However, mothers delivering by caesarean section routinely receive prophylactic antibiotics prior to delivery, resulting in antibiotic exposure to the infant via the placenta. Previously, only a small number of studies have examined the effect of delivery mode versus antibiotic exposure on the infant gut microbiome with mixed findings. Objective. We aimed to determine the effect of delivery mode compared to antibiotic use during labour and delivery on the infant and maternal gut microbiome at 6 weeks post-partum. Methodology. Twenty-five mother-infant dyads were selected from the longitudinal Queensland Family Cohort Study. The selected dyads comprised nine vaginally delivered infants without antibiotics, seven vaginally delivered infants exposed to antibiotics and nine infants born by caesarean section with routine maternal prophylactic antibiotics. Shotgun-metagenomic sequencing of DNA from stool samples collected at 6 weeks post-partum from mother and infant was used to assess microbiome composition. Results. Caesarean section infants exhibited decreases in Bacteroidetes (ANCOM-BC q <0.0001, MaAsLin 2 q =0.041), changes to several functional pathways and altered beta diversity ( R 2 =0.056, P= 0.029), while minimal differences due to antibiotic exposure were detected. For mothers, caesarean delivery ( P= 0.0007) and antibiotic use ( P =0.016) decreased the evenness of the gut microbiome at 6 weeks post-partum without changing beta diversity. Several taxa in the maternal microbiome were altered in association with antibiotic use, with few differentially abundant taxa associated with delivery mode. Conclusion. For infants, delivery mode appears to have a larger effect on gut microbiome composition at 6 weeks post-partum than intrapartum antibiotic exposure. For mothers, both delivery mode and intrapartum antibiotic use have a small effect on gut microbiome composition at 6 weeks post-partum.

Introduction: Previous studies have reported that neonates less than the 25th BWC especially if they were male, were more likely to be associated with birth complications suggesting small neonates often identified as appropriately grown are at risk of adverse outcomes. We have questioned whether smaller neonates not typically categorized as "small for gestational age" may not reach their genetically determined growth due to placental insufficiency., Methods: RNA-Seq was performed on the Illumina NovaSeq 600 using term placentae from neonates that were less than the 10th birthweight centile (BWC) (n = 39), between the 10th and the 30th BWC (n = 15) or greater than the 30th BWC (n = 23). Bioinformatic analyses were conducted and statistical significance was assessed at a level of P < 0.05 for single comparisons or FDR <0.05 unless otherwise noted., Results: Gene set enrichment analysis revealed differences between BWC groups and in relation to the sex of the placenta. Genes associated with hypoxia, inflammatory responses, estrogen responsive genes, and androgen responsive genes were enriched (FDR <0.1) for in placentae of neonates <10th BWC regardless of sex and also in male placentae of neonates between the 10th-30th BWC. Female placenta of neonates between the 10th-30th BWC were comparable to placentae of neonates >30th BWC., Discussion: These findings provide evidence that small male neonates may be at a greater risk of an adverse outcome than females due to changes in gene expression that are associated with placental dysfunction. The current data raises questions of whether placental pathology for smaller appropriately grown neonates should be scientifically and clinically examined in more depth., Competing Interests: Declaration of Competing interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Introduction: Preeclampsia is a common hypertensive disorder of pregnancy. Several studies have demonstrated that protein aggregates, detected through urine congophilia, is associated with preeclampsia; however, it has yet to be investigated whether urine congophilia remains postpartum in these women. In this study, we aimed to augment prior studies and determine whether urine congophilia is present postpartum., Methods: Women were recruited from Lyell McEwin Hospital, South Australia. Urine samples were collected during pregnancy and 6-months postpartum from women with non-preeclampsia pregnancies (n = 48) and women with pregnancies complicated by preeclampsia (n = 42). A Congo Red Dot blot test, total protein and creatinine levels from urine, as well as serum Soluble fms-like tyrosine kinase 1 to placental growth factor ratio (sFlt-1:PlGF), were assessed and correlated., Results: Preeclamptic women exhibited increased urine congophilia (P < 0.01), sFlt-1:PlGF ratio (P < 0.0001) and total protein (P < 0.01) during pregnancy; with a positive correlation between urine congophilia and total protein across the entire cohort (P < 0.0001). Although urine congophilia was no longer detected 6-months postpartum in preeclamptic women, total protein remained elevated (P < 0.05). sFlt-1:PlGF ratio during pregnancy was positively correlated with congophilia across the cohort (P = 0.0007). Serum creatinine was also higher in preeclamptic women during pregnancy (P < 0.001)., Discussion: These results support that urine congophilia is significantly elevated in pregnancies complicated with preeclampsia and show that it does not continue postpartum, although larger cohort studies are needed to determine its feasibility as a diagnostic marker., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There is an increased risk of adverse perinatal outcomes in the ∼17% of women with asthma during pregnancy. The mechanisms linking maternal asthma and adverse outcomes are largely unknown, but reflect joint effects of genetics and prenatal exposure to maternal asthma. Animal models are essential to understand the underlying mechanisms independent of genetics and comorbidities, and enable safe testing of interventions. This scoping review aimed to explore the methodology, phenotype, characteristics, outcomes and quality of published studies using preclinical maternal asthma models. MEDLINE (PubMed), Embase (Elsevier) and Web of Science were systematically searched using previously validated search strings for maternal asthma and for animal models. Two reviewers independently screened titles and abstracts, full texts, and then extracted and assessed the quality of each study using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) 2.0 guidelines. Out of 3618 studies identified, 39 were eligible for extraction. Most studies were in rodents (86%) and all were models of allergic asthma. Maternal and progeny outcomes included airway hyperresponsiveness, airway resistance, inflammation, lung immune cells, lung structure and serum immunoglobulins and cytokines. Experimental design (100%), procedural details (97%) and rationale (100%) were most often reported. Conversely, data exclusion (21%), blinding (18%) and adverse events (8%) were reported in a minority of studies. Species differences in physiology and timing of development, the use of allergens not relevant to humans and a lack of comparable outcome measures may impede clinical translation. Future studies exploring models of maternal asthma should adhere to the minimum core outcomes set presented in this review., Competing Interests: Conflict of interest: The authors declare no conflicts of interest., (Copyright ©The authors 2024.)

Introduction: Sex differences in prenatal growth may contribute to sex-dependent programming effects on postnatal phenotype., Methods: We integrated for the first time phenotypic, histomorphological, clinico-chemical, endocrine and gene expression analyses in a single species, the bovine conceptus at mid-gestation., Results: We demonstrate that by mid-gestation, before the onset of accelerated growth, the female conceptus displays asymmetric lower growth compared to males. Female fetuses were smaller with lower ponderal index and organ weights than males. However, their brain:body weight, brain:liver weight and heart:body weight ratios were higher than in males, indicating brain and heart 'sparing'. The female placenta weighed less and had lower volumes of trophoblast and fetal connective tissue than the male placenta. Female umbilical cord vessel diameters were smaller, and female-specific relationships of body weight and brain:liver weight ratios with cord vessel diameters indicated that the umbilico-placental vascular system creates a growth-limiting environment where blood flow is redistributed to protect brain and heart growth. Clinico-chemical indicators of liver perfusion support this female-specific growth-limiting phenotype, while lower insulin-like growth factor 2 (IGF2) gene expression in brain and heart, and lower circulating IGF2, implicate female-specific modulation of key endocrine mediators by nutrient supply., Conclusion: This mode of female development may increase resilience to environmental perturbations in utero and contribute to sex-bias in programming outcomes including susceptibility to non-communicable diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Estrella, Gatford, Xiang, Javadmanesh, Ghanipoor-Samami, Nattrass, Shuaib, McAllister, Beckman, Thomsen, Clifton, Owens, Roberts, Hiendleder and Kind.)

A birthweight centile (BWC) below the 25th is associated with an elevated risk of adverse perinatal outcomes, particularly among males. This male vulnerability may stem from alterations in placenta-specific androgen signalling, a signalling axis that involves the androgen receptor (AR)-mediated regulation of target genes containing androgen response elements (AREs). In this study, we examined global and ARE-specific transcriptomic signatures in term male placentae (≥37 weeks of gestation) across BWC subcategories (<10th, 10th-30th, >30th) using RNA-seq and gene set enrichment analysis. ARE-containing transcripts in placentae with BWCs below the 10th percentile were upregulated compared to those in the 10th-30th and >30th percentiles, which coincided with the enrichment of gene sets related to hypoxia and the suppression of gene sets associated with mitochondrial function. In the absence of ARE-containing transcripts in silico, <10th and 10th-30th BWC subcategory placentae upregulated gene sets involved in vasculature development, immune function, and cell adhesion when compared to those in the >30th BWC subcategory. Collectively, our in silico findings suggest that changes in the expression of ARE-containing transcripts in male placentae may contribute to impaired placental vasculature and therefore result in reduced fetal growth outcomes.

Background: Maternal obesity (MO) increases fetal androgen concentrations, the prevalence of macrosomia, and predisposes offspring to metabolic dysfunction in later life, especially males. These risks may be, in part, the result of increased liver-specific androgen signalling pathway activity in utero. Androgen signalling activity can be suppressed by androgen metabolism via cytochrome P450 (CYP) isoenzymes (CYP2B6, CYP3A) or through inhibition of the full-length androgen receptor (AR-FL) via the antagonistic isoform, AR-45. We hypothesised MO impairs CYP enzyme activity and AR-45 expression in male fetal livers, thereby enhancing activity of androgen signalling pathways., Methods: Nine months prior to pregnancy, nulliparous female baboons were assigned to either ad libitum control or high fat diet. At 165 day (d) gestation (term, 180 d) fetal liver was collected (n = 6/sex/group). CYP activity was quantified using functional assays; subcellular AR expression was measured using Western blot., Results: CYP2B6 and CYP3A activity, and nuclear expression of AR-45, was reduced in MO males only. Nuclear AR-45 expression was inversely related with fetal body weight of MO males only., Conclusions: Reduced CYP2B6 and CYP3A activity in conjunction with decreased nuclear AR-45 expression may enhance liver androgen signalling in males from MO pregnancies, thereby increasing the risk of macrosomia, as well as metabolic dysfunction in later life., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In high-income nations, multiple micronutrient (MMN) supplementation during pregnancy is a common practice. We aimed to describe maternal characteristics associated with supplement use and daily dose of supplemental nutrients consumed in pregnancy, and whether guideline alignment and nutrient status are related to supplement use. The Queensland Family Cohort is a prospective, Australian observational longitudinal study. Maternal characteristics, nutrient intake from food and supplements, and biochemical nutrient status were assessed in the second trimester (n = 127). Supplement use was reported by 89% of participants, of whom 91% reported taking an MMN supplement. Participants who received private obstetric care, had private health insurance and had greater alignment to meat/vegetarian alternatives recommendations were more likely to report MMN supplement use. Private obstetric care and general practitioner shared care were associated with higher daily dose of supplemental nutrients consumed compared with midwifery group practice. There was high reliance on supplements to meet nutrient reference values for folate, iodine and iron, but only plasma folate concentrations were higher in MMN supplement versus nonsupplement users. Exceeding the upper level of intake for folic acid and iron was more likely among combined MMN and individual supplement/s users, and associated with higher plasma concentrations of the respective nutrients. Given the low alignment with food group recommendations and potential risks associated with high MMN supplement use, whole food diets should be emphasized. This study confirms the need to define effective strategies for optimizing nutrient intake in pregnancy, especially among those most vulnerable where MMN supplement use may be appropriate., (© 2023 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: Genome-wide DNA methylation (DNAme) profiling of the placenta with Illumina Infinium Methylation bead arrays is often used to explore the connections between in utero exposures, placental pathology, and fetal development. However, many technical and biological factors can lead to signals of DNAme variation between samples and between cohorts, and understanding and accounting for these factors is essential to ensure meaningful and replicable data analysis. Recently, "epiphenotyping" approaches have been developed whereby DNAme data can be used to impute information about phenotypic variables such as gestational age, sex, cell composition, and ancestry. These epiphenotypes offer avenues to compare phenotypic data across cohorts, and to understand how phenotypic variables relate to DNAme variability. However, the relationships between placental epiphenotyping variables and other technical and biological variables, and their application to downstream epigenome analyses, have not been well studied., Results: Using DNAme data from 204 placentas across three cohorts, we applied the PlaNET R package to estimate epiphenotypes gestational age, ancestry, and cell composition in these samples. PlaNET ancestry estimates were highly correlated with independent polymorphic ancestry-informative markers, and epigenetic gestational age, on average, was estimated within 4 days of reported gestational age, underscoring the accuracy of these tools. Cell composition estimates varied both within and between cohorts, as well as over very long placental processing times. Interestingly, the ratio of cytotrophoblast to syncytiotrophoblast proportion decreased with increasing gestational age, and differed slightly by both maternal ethnicity (lower in white vs. non-white) and genetic ancestry (lower in higher probability European ancestry). The cohort of origin and cytotrophoblast proportion were the largest drivers of DNAme variation in this dataset, based on their associations with the first principal component., Conclusions: This work confirms that cohort, array (technical) batch, cell type proportion, self-reported ethnicity, genetic ancestry, and biological sex are important variables to consider in any analyses of Illumina DNAme data. We further demonstrate the specific utility of epiphenotyping tools developed for use with placental DNAme data, and show that these variables (i) provide an independent check of clinically obtained data and (ii) provide a robust approach to compare variables across different datasets. Finally, we present a general framework for the processing and analysis of placental DNAme data, integrating the epiphenotype variables discussed here., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: Asthma occurs in ∼17% of Australian pregnancies and is associated with adverse perinatal outcomes, which worsen with poor asthma control. Consequently, the South Australian 'Asthma in Pregnancy' perinatal guidelines were revised in 2012 to address management according to severity. This study investigated if these revised guidelines reduced the impact of maternal asthma on risks of adverse perinatal outcomes before (Epoch 1, 2006-2011) and after the revision (Epoch 2, 2013-2018)., Methods: Routinely collected perinatal and neonatal datasets from the Women's and Children's Hospital (Adelaide, Australia) were linked. Maternal asthma (prevalence:7.5%) was defined as asthma medication use or symptoms described to midwives. In imputation ( n  = 59131) and complete case datasets ( n  = 49594), analyses were conducted by inverse proportional weighting and multivariate logistic regression, accounting for confounders., Results: Overall, maternal asthma was associated with increased risks of any antenatal corticosteroid treatment for threatened preterm birth (aOR 1.319, 95% CI 1.078-1.614), any Cesarean section (aOR 1.196, 95% CI 1.059-1.351), Cesarean section without labor (aOR 1.241, 95% CI 1.067-1.444), intrauterine growth restriction (IUGR, aOR 1.285, 95% CI 1.026-1.61), and small for gestational age (aOR 1.324, 95% CI 1.136-1.542). After guideline revision, asthma-associated risks of any Cesarean section ( p  < 0.001), any antenatal corticosteroids ( p  = 0.041), and small for gestational age ( p  = 0.050), but not IUGR and Cesarean section without labor, were reduced., Conclusions: Clinical practice guidelines based on the latest evidence do not guarantee clinical efficacy. Since adverse perinatal outcomes did not all improve, this work highlights the need to evaluate the ongoing impact of guidelines on clinical outcomes.

Background: There is growing evidence regarding the potential of closed incision negative pressure wound therapy (ci-NPWT) to prevent surgical site infections (SSIs) in healing wounds by primary closure following a caesarean section (CS)., Aim: To assess the cost-effectiveness of ci-NPWT compared to standard dressings for prevention of SSI in obese women giving birth by CS., Materials and Methods: Cost-effectiveness and cost-utility analyses from a health service perspective were undertaken alongside a multicentre pragmatic randomised controlled trial, which recruited women with a pre-pregnancy body mass index ≥30 kg/m 2 giving birth by elective/semi-urgent CS who received ci-NPWT (n = 1017) or standard dressings (n = 1018). Resource use and health-related quality of life (SF-12v2) collected during admission and for four weeks post-discharge were used to derive costs and quality-adjusted life years (QALYs)., Results: ci-NPWT was associated with AUD$162 (95%CI -$170 to $494) higher cost per person and an additional $12 849 (95%CI -$62 138 to $133 378) per SSI avoided. There was no detectable difference in QALYs between groups; however, there are high levels of uncertainty around both cost and QALY estimates. There is a 20% likelihood that ci-NPWT would be considered cost-effective at a willingness-to-pay threshold of $50 000 per QALY. Per protocol and complete case analyses gave similar results, suggesting that findings are robust to protocol deviators and adjustments for missing data., Conclusions: ci-NPWT for the prevention of SSI in obese women undergoing CS is unlikely to be cost-effective in terms of health service resources and is currently unjustified for routine use for this purpose., (© 2023 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: This scoping review will describe the methodology, phenotype, and characteristics of maternal asthma models used in preclinical studies and the outcomes that have been measured in the mother and progeny. The review This will identify gaps in knowledge of maternal and progeny outcomes following maternal asthma in pregnancy., Introduction: Maternal asthma affects up to 17% of pregnancies worldwide and is associated with adverse perinatal outcomes in mothers and babies, including pre-eclampsia, gestational diabetes, cesarean section, preterm birth, small for gestational age, nursery admission, and neonatal death. While the associations are well established, the mechanisms linking maternal asthma and adverse perinatal outcomes are largely unknown due to the difficulties of human mechanistic studies. The appropriate selection of animal models is vital to understanding the mechanisms underlying associations between human maternal asthma and adverse perinatal outcomes., Inclusion Criteria: This review will include primary studies published in English where outcomes have been studied in vivo in non-human mammalian species., Methods: This review will follow the JBI methodology for scoping reviews. We will search MEDLINE (PubMed), Embase, and Web of Science to identify papers published before the end of 2022. Initial keywords will include pregnancy, gestation, asthma , and wheeze , as well as validated search strings to identify papers that describe animal models. Extracted data will include information on methods used to induce maternal asthma; asthmatic phenotypes and characteristics; and maternal, pregnancy, placental, and progeny outcomes. The characteristics of each study will be presented in summary tables and a core outcome list to assist researchers in developing, reporting, and comparing future animal studies of maternal asthma., Review Registration: Open Science Framework osf.io/trwk5., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 JBI.)

Alterations in the hypothalamic-pituitary-adrenal (HPA) axis and associated changes in circulating levels of glucocorticoids are integral to an organism's response to stressful stimuli. Glucocorticoids acting via glucocorticoid receptors (GRs) play a role in fertility, reproduction, placental function, and foetal development. GRs are ubiquitously expressed throughout the female reproductive system and regulate normal reproductive function. Stress-induced glucocorticoids have been shown to inhibit reproduction and affect female gonadal function by suppressing the hypothalamic-pituitary-gonadal (HPG) axis at each level. Furthermore, during pregnancy, a mother's exposure to prenatal stress or external glucocorticoids can result in long-lasting alterations to the foetal HPA and neuroendocrine function. Several GR isoforms generated via alternative splicing or translation initiation from the GR gene have been identified in the mammalian ovary and uterus. The GR isoforms identified include the splice variants, GRα and GRβ, and GRγ and GR-P. Glucocorticoids can exert both stimulatory and inhibitory effects and both pro- and anti-inflammatory functions in the ovary, in vitro. In the placenta, thirteen GR isoforms have been identified in humans, guinea pigs, sheep, rats, and mice, indicating they are conserved across species and may be important in mediating a differential response to stress. Distinctive responses to glucocorticoids, differential birth outcomes in pregnancy complications, and sex-based variations in the response to stress could all potentially be dependent on a particular GR expression pattern. This comprehensive review provides an overview of the structure and function of the GR in relation to female fertility and reproduction and discusses the changes in the GR and glucocorticoid signalling during pregnancy. To generate this overview, an extensive non-systematic literature search was conducted across multiple databases, including PubMed, Web of Science, and Google Scholar, with a focus on original research articles, meta-analyses, and previous review papers addressing the subject. This review integrates the current understanding of GR variants and their roles in glucocorticoid signalling, reproduction, placental function, and foetal growth.

Objective: Asthma and obesity are both inflammatory complications of pregnancy and when combined contribute to an increased risk of uncontrolled asthma during pregnancy and poor perinatal outcomes. Our previous work has identified the presence of maternal asthma is associated with a proinflammatory milieu in the placenta and reduced fetal growth. The current study was designed to determine the relationships between immunomodulatory metabolic pathways and inflammation and establish whether these pathways are associated with uncontrolled asthma in obese pregnant women., Methods: Fifty-three obese (BMI >30) pregnant women were recruited prospectively. Participants were classified as having no asthma, controlled asthma, and uncontrolled asthma based on a doctor diagnosis and assessment using the Asthma Control Questionnaire (ACQ). Circulating plasma concentrations of metabolic hormones leptin, adiponectin, insulin, glucose, and extracellular vesicle (EVs) associated cytokines were measured at 18- and 36-weeks gestation., Results: Concentrations of metabolic and inflammatory markers among obese participants with or without asthma were not significantly different throughout gestation. However total adiponectin concentrations increased as gestation progressed in obese, non-asthmatic women but did not increase in women with asthma. Plasma adiponectin and leptin levels in women with uncontrolled asthma were positively correlated with EV inflammatory markers including GM-CSF, IL-6, TNFα and IFNγ protein., Conclusions: This study demonstrated that most metabolic markers remain unchanged with the presence and severity of asthma in obese pregnant women. However, differences in the associations between metabolic and inflammatory pathways were observed in women with asthma and may be one of the mechanisms contributing to uncontrolled asthma in obese pregnant women.

Antenatal depression (AND) affects 1 in 10 fathers, potentially negatively impacting maternal mental health and well-being during and after the transition to parenthood. However, few studies have assessed the social predictors of paternal AND or their possible associations with maternal mental health. We analysed data from 180 couples participating in the Queensland Family Cohort longitudinal study. Both parents completed surveys measuring mental health, relationship quality, social support, and sleep quality at 24 weeks of pregnancy. Mothers also completed the same surveys 6 weeks' postpartum. Antenatal depression, stress, and anxiety were highest among fathers reporting lower social support and higher sleep impairment. Maternal AND, stress, and anxiety were higher among mothers reporting higher physical pain and poor sleep quality. Postnatally, mothers reporting lower social support also reported higher depression, anxiety, stress, and psycho-social well-being. While there were no significant associations between AND among fathers and maternal antenatal or postnatal depression, an exploratory analysis revealed that mothers whose partners reported lower antenatal social support also reported lower postnatal social support and higher postnatal depression. Our findings highlight the importance of including data among fathers to achieve a whole family approach to well-being during the transition to parenthood., (© 2022. The Author(s).)

Breastmilk is thought to influence the infant gut by supplying prebiotics in the form of human milk oligosaccharides and potentially seeding the gut with breastmilk microbes. However, the presence of a breastmilk microbiota and origins of these microbes are still debated. As a pilot study, we assessed the microbes present in expressed breastmilk at six-weeks postpartum using shotgun metagenomic sequencing in a heterogenous cohort of women who delivered by vaginal (n = 8) and caesarean delivery (n = 8). In addition, we estimated the microbial load of breastmilk at six-weeks post-partum with quantitative PCR targeting the 16S rRNA gene. Breastmilk at six-weeks postpartum had a low microbial mass, comparable with PCR no-template and extraction controls. Microbes identified through metagenomic sequencing were largely consistent with skin and oral microbes, with four samples returning no identifiable bacterial sequences. Our results do not provide convincing evidence for the existence of a breastmilk microbiota at six-weeks postpartum. It is more likely that microbes present in breastmilk are sourced by ejection from the infant's mouth and from surrounding skin, as well as contamination during sampling and processing.

Introduction: Ultrasound elastography shows diagnostic promise via the non-invasive determination of placental elastic properties. A limitation is a potential for inadequate measurements from posterior placentae. This study aimed to analyse placental position's influence on measures of shear wave elastography (SWV)., Methods: SWV elastography measurements were obtained via ultrasound at 24, 28 and 36 weeks gestation from 238 pregnancies. . The placental position was labelled as either anterior, posterior or fundal/lateral. Average SWV measurements (m/s) and the corresponding standard deviations (SD) were used for data analysis., Results: There was a statistically significant difference between SWV recorded from anterior (1.33 ± 0.19)m/s and posterior (1.39 ± 0.18)m/s placentae (p < 0.001). However, the average sampling depth between these groups was significantly different (3.98 cm vs. 5.38 cm, p < 0.001). There was no statistically significant difference between SWV when measurements were compared at similar depths, regardless of placental location. The addition of placental position to a previously developed mixed-effects model confirmed placental position did not result in improved SWV measurements. In this model, sampling depth remained the best predictor for SWV., Conclusions: This study showed that placental position does not influence the accuracy or reliability of SWV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: The pathological decrease of fetal growth during gestation can lead to subsequent poor health outcomes for the fetus. This process is commonly controlled by the placenta, the interface between mother and baby during gestation. Sex-specific gene expression has been implicated in placental function, therefore, there is a need to determine if it is important during reduced fetal growth. We therefore aimed to characterise placental gene expression at term to evaluate sex-specific genetic changes that occur in small for gestational age (SGA) infants., Methods: RNA-sequencing of twelve human placental tissue samples collected from pregnancies yielding either term appropriate for gestational age (AGA) or SGA infants identified at delivery. Candidate genes associated with fetal size and fetal sex were identified using differential gene expression and weighted gene co-expression network analyses. Single-cell sequencing data was used for candidate validation and to estimate candidate transcript expression in specific placental cell populations., Results: Differential gene expression and weighted gene co-expression network analyses identified 403 candidate transcripts associated with SGA infants. One hundred and three of these transcripts showed sex-specific expression. . Published placental sequencing datasets were used to validate the key expression results from the twelve placental samples initially studied; the sex-independent transcript expression for genes involved in cell cycle processes in males (7 transcripts) and endoplasmic reticulum stress in females (17 transcripts)., Discussion: This study identified the activation of multiple molecular mechanisms involved in the placental response to an adverse environmental stressor. Mechanisms such as disrupted protein synthesis were shared between infant biological sex when comparing AGA to SGA, whilst other pathways such as cell cycle and endoplasmic reticulum stress appear as independent/specific to either males or females when investigating reduced fetal growth. This data suggests that sexual dimorphism is an important consideration when examining placental dysfunction and poor fetal growth., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Asthma during pregnancy and extremes of body mass index (BMI) are independently associated with adverse pregnancy outcomes but the impact of the two conditions combined are currently unknown. The aim of this study was to determine the contribution of maternal BMI to adverse birth outcomes in pregnancies complicated by asthma., Methods: The study utilized the routinely collected perinatal data on births at the Mater Mother's Hospital Brisbane, Australia, from January 2008 to December 2019. BMI was grouped as underweight (&lt;18.5), normal weight (18.5-&lt;24.99), overweight (25-29.99), and obese (≥30) and the population split by the presence and absence of maternal asthma. The comparison group was normal BMI, non-asthmatic pregnant women. A modified Poisson regression with robust variance was used to estimate the relative risk., Results: In a retrospective cohort study of 110,057 pregnant women, 17.08% of women had asthma. Asthma and BMI were associated with an increased risk of poor fetal and neonatal outcomes. Asthma significantly increased the risk of stillbirth in underweight [adjusted RR: 2.22 (95% CI: 1.25-3.94] and obese [1.74 (1.11-2.71)]; neonatal death in underweight [3.41 (1.89-6.16)] and obese [2.22 (1.37-3.59)] and perinatal death in underweight [2.34 (1.50-3.66)] and obese [1.92 (1.38-2.67)] women. Admission to the neonatal intensive care unit was increased in neonates of underweight [1.65 (1.44-1.89)] and obese [1.26 (1.14-1.40)] asthmatic women., Conclusions: Extremes of BMI, specifically underweight and obesity, increased the risk of adverse perinatal outcomes among asthmatic women highlighting the importance of accounting for BMI during pre-conception and pregnancy related management of asthmatic women.

Background: There are very few developed countries where physical isolation and low community transmission has been reported for COVID-19 but this has been the experience of Australia. The impact of physical isolation combined with low disease transmission on the mental health of pregnant women is currently unknown and there have been no studies examining the psychological experience for partners of pregnant women during lockdown. The aim of the current study was to examine the impact of the first COVID-19 lockdown in March 2020 and post lockdown from August 2020 on the mental health of pregnant women or postpartum women and their partners., Methods: Pregnant women and their partners were prospectively recruited to the study before 24 weeks gestation and completed various questionnaires related to mental health and general wellbeing at 24 weeks gestation and then again at 6 weeks postpartum. The Depression, Anxiety and Stress Scale (DASS-21) and the Edinburgh Postnatal Depression Scale (EPDS) were used as outcome measures for the assessment of mental health in women and DASS-21 was administered to their partners. This analysis encompasses 3 time points where families were recruited; before the pandemic (Aug 2018-Feb 2020), during lockdown (Mar-Aug 2020) and after the first lockdown was over (Sept-Dec 2020)., Results: There was no significant effect of COVID-19 lockdown and post lockdown on depression or postnatal depression in women when compared to a pre-COVID-19 subgroup. The odds of pregnant women or postpartum women experiencing severe anxiety was more than halved in women during lockdown relative to women in the pre-COVID-19 period (OR = 0.47; 95%CI: 0.27-0.81; P = 0.006). Following lockdown severe anxiety was comparable to the pre-COVID-19 women. Lockdown did not have any substantial effects on stress scores for pregnant and postpartum women. However, a substantial decrease of over 70% in the odds of severe stress was observed post-lockdown relative to pre-COVID-19 levels. Partner's depression, anxiety and stress did not change significantly with lockdown or post lockdown., Conclusion: A reproductive age population appear to be able to manage the impact of lockdown and the pandemic with some benefits related to reduced anxiety., (© 2022. The Author(s).)

Expression of allergic diseases in very early childhood indicates that early life events play a significant role in childhood allergy development. The developmental origins of allergy hypothesis suggest events initiated in the in-utero period derived from the interaction between maternal, placental, and fetal factors may contribute to childhood allergy susceptibility. Environmental impacts on placental function and fetal programming are imperative in defining illness risk during pregnancy. Fetal programming, a process by which an injury delivered during a critical period of development, causes immediate adaptive responses with long-term consequences on an organism's structure or function. During pregnancy, the maternal immune response is skewed towards Th2-related humoral responses, hence increasing the susceptibility of childhood allergy development. Maternal atopic phenotype markedly increases the probability of her offspring developing an allergic predisposition. Combination of in utero events - which include maternal asthma or infection, and exposures to maternal allergy which changes the placental function - can alter placental cytokine expression and could predispose offspring to an allergic phenotype. All these events may affect embryology and fetal immune system development. Interestingly, the mechanism and role of the in-utero events on the developmental origins of allergy are not clearly understood; this will be addressed in this review. (199 words)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Society for Histocompatibility and Immunogenetics. All rights reserved.)