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Mitochondrial donation to reduce the risk of primary mitochondrial disease transmission from mother to child is now permitted under Australian law as part of a clinical trial. The energy demands of pregnancy have the potential to worsen mitochondrial disease symptoms and severity in affected women. We conducted a systematic literature review on mitochondrial disease in pregnancy; five cohort studies and 19 case reports were included. For many women with mitochondrial disease, pregnancy does not have a negative effect on health status. However, serious adverse outcomes may occur. We provide suggested guidelines for preconception counselling and antenatal care. [ABSTRACT FROM AUTHOR]

Objective This study aimed to investigate human fetal exposure to non-nutritive sweeteners (NNS) by analyzing amniotic fluid and umbilical cord blood. Study Design Concentrations of four NNS (acesulfame-potassium [ace-K], saccharin, steviol glucuronide, and sucralose) were measured in amniotic fluid (n = 13) and cord blood samples (n = 15) using liquid chromatography-mass spectrometry. Amniotic fluid samples were obtained for research purposes at the time of term elective cesarean birth or clinically indicated third trimester amnioreduction at Mercy Hospital for Women (Melbourne, Australia). All except four women were in the fasting state. Cord blood samples were obtained from an independent cohort of newborns whose mothers were enrolled in a separate clinical trial at the National Institutes of Health. Results Ten of 13 amniotic fluid samples contained at least one NNS (ace-K, saccharin, steviol glucuronide, and/or sucralose). Maximum amniotic fluid NNS concentrations of ace-K, saccharin, steviol glucuronide, and sucralose were 78.9, 55.9, 93.5, and 30.6 ng/mL, respectively. Ace-K and saccharin were present in 100% and 80% of the cord blood samples, with maximal concentrations of 6.5 and 2.7 ng/mL, respectively. Sucralose was not detected and steviol glucuronide was not measurable in any of the cord blood samples. Conclusion Our results provide evidence of human transplacental transmission of NNS. Based on results predominantly obtained from rodent models, we speculate that NNS exposure may adversely influence the offsprings' metabolic health. Well-designed, prospective clinical trials are necessary to understand the impact of NNS intake during pregnancy on human development and long-term health. Key Points NNS consumption during pregnancy has increased in recent years. Maternal NNS intake during pregnancy is associated with preterm birth and higher infant weight gain in epidemiologic studies. In rodents, in utero NNS exposure induces metabolic abnormalities in mothers and their offspring, alters offspring gut microbiota composition, and promotes sweet taste preference in adulthood. It is presently unknown whether and to what degree maternal NNS ingestion in humans leads to direct in utero exposure. This study provides the first evidence of in utero NNS exposure in humans and highlights the urgent need to investigate clinical consequences of early life NNS exposure on metabolism, weight, taste preference, and general health. [ABSTRACT FROM AUTHOR]

Little is published on cytomegalovirus (CMV) serological screening at the first antenatal visit or the contemporary CMV seroprevalence rates among the Australian pregnant population. We performed a retrospective analysis of public hospital births in a major tertiary centre (n = 840) over a two month period. We found that 13.6% (95% confidence interval (CI) 11.4–16.1%) of women had been screened for CMV at their first antenatal visit with their general practitioner. Of these, 43.0% (95% CI 34.3–52.1%) were CMV seronegative and therefore susceptible to primary infection. Seronegative women were also more likely to have been born in an economically developed country, to live in a socio‐economically advantaged postcode and to be nulliparous. The information from this study may help guide future studies of congenital CMV risk reduction strategies. [ABSTRACT FROM AUTHOR]

Prenatal screening for aneuploidy has undergone immense changes over the past two decades. In 2013 cell‐free DNA‐based non‐invasive prenatal testing (NIPT) became a new self‐funded option primarily for Down syndrome screening, but also other aneuploidies and genetic conditions. The numbers of Medicare item claims for prenatal diagnostic procedures have halved since the introduction of NIPT, while billings for serum screening fell by 40% over the same period, on a background of steady births. Australia is now observing historically low rates of prenatal diagnostic testing. These data provide an informative snapshot of historic changes in prenatal screening and diagnosis, as our sector prepares for the impending impacts of other advances in genomics on maternity care. They also highlight the need to address equity and quality issues that arise when consumers must bear the full costs of improved genomic tests in the absence of Medicare funding. [ABSTRACT FROM AUTHOR]

Risk assessment for venous thromboembolism in pregnancy and the puerperium is currently limited to stratifying clinical surrogate risk factors without high-quality evidence. While the absolute risk of pregnancy-associated venous thromboembolism is low for the vast majority of women, associated morbidity and mortality remains significant. As guidelines for thromboprophylaxis vary widely, some women may be under- or over-anticoagulated, contributing to poor outcomes. New global coagulation assays provide a holistic view of coagulation and may have the potential to detect hypercoagulability in pregnancy, unlike clinically available coagulation assays. However, there are major technical challenges to overcome before global coagulation assays can be realistically proposed as an adjunct to risk assessment for pregnancy-associated venous thromboembolism. This review summarises the literature and controversies in the prediction and prevention of pregnancy-associated venous thromboembolism and outlines the new tools in haematology that may assist in our future understanding of hypercoagulability in pregnancy. [ABSTRACT FROM AUTHOR]

Previously, we identified elevated transcripts for the gene Oleoyl-ACP Hydrolase (OLAH) in the maternal circulation of pregnancies complicated by preterm fetal growth restriction. As placental dysfunction is central to the pathogenesis of both fetal growth restriction and preeclampsia, we aimed to investigate OLAH levels and function in the human placenta. We assessed OLAH mRNA expression (qPCR) throughout pregnancy, finding placental expression increased as gestation progressed. OLAH mRNA and protein levels (Western blot) were elevated in placental tissue from cases of preterm preeclampsia, while OLAH protein levels in placenta from growth-restricted pregnancies were comparatively reduced in the preeclamptic cohort. OLAH expression was also elevated in placental explant tissue, but not isolated primary cytotrophoblast cultured under hypoxic conditions (as models of placental dysfunction). Further, we discovered that silencing cytotrophoblast OLAH reduced the expression of pro- and anti-apoptosis genes, BAX and BCL2, placental growth gene, IGF2, and oxidative stress gene, NOX4. Collectively, these findings suggest OLAH could play a role in placental dysfunction and may be a therapeutic target for mitigating diseases associated with this vital organ. Further research is required to establish the role of OLAH in the placenta, and whether these changes may be a maternal adaptation or consequence of disease. [ABSTRACT FROM AUTHOR]

Introduction: Women are at higher risk of venous thromboembolism (VTE) during pregnancy and the puerperium. Global coagulation assays (GCAs), including thromboelastography (TEG), thrombin generation using the calibrated automated thrombogram (CAT) and fibrin generation using the overall haemostatic potential assay (OHP), provide a more comprehensive assessment of the coagulation process than conventional coagulation assays. We aimed to evaluate the ability of these GCAs to analyse the coagulability among pregnant women of varying VTE risk profile. Methods: Women undergoing term elective caesarean delivery provided a single predelivery blood sample for conventional and novel coagulation testing (TEG, CAT and OHP). Data from 47 healthy nonpregnant women aged 18‐45 years were used as controls. Results: Sixty women with term singleton pregnancies were included. Samples from pregnant women were hypercoagulable on most GCA parameters compared to nonpregnant controls, demonstrating increased maximum amplitude (clot strength) (71.5 vs 60.6 mm, P <.001) on whole blood TEG and increased endogenous thrombin potential (1895.22 vs 1399.33 nmol/L·min, P <.001) and overall coagulation potential (fibrin generation) (57.58 vs 36.21 units, P <.001) on platelet‐poor plasma. Pregnant women with booking BMI ≥ 30 kg/m2 had significantly higher maximum amplitude compared to pregnant women of normal BMI (18.5‐25 kg/m2) (73.2 vs 66.1 mm, P <.001). Conclusions: Global coagulation assays reliably detect the physiological hypercoagulability of pregnancy. Thromboelastography in particular appears to correlate with obesity in the pregnant population. GCAs may be potential adjuncts to risk factor‐based criteria to guide VTE thromboprophylaxis during pregnancy and the puerperium. [ABSTRACT FROM AUTHOR]

Background: Small for gestational age (SGA) is a major determinant of poor perinatal outcome. Detecting SGA at term using ultrasound is challenging and we often plan birth based on clinical assessment. Aims: To determine the incidence of SGA infants with birthweight <10th centile among women undergoing planned birth at term for suspected SGA despite a normal estimated fetal weight (EFW) on ultrasound at 35–37 weeks. Materials and Methods: We performed a retrospective study including all women with a fetal growth ultrasound at ≥35 weeks reporting an EFW ≥ 10th centile (appropriate for gestational age, AGA) who subsequently had an induction of labour or caesarean birth at ≥37 weeks due to ongoing clinical suspicion of SGA between 2012–2014. The primary outcome was the incidence of SGA newborns using customised centiles. Results: There were 532 women who had a planned birth for clinical suspicion of SGA during the study period. Of these, 205 (38.5%) had an AGA fetus on ultrasound ≥35 weeks but were subsequently delivered because of a persisting clinical suspicion of SGA on abdominal assessment. Sixty‐eight percent (n = 139/205) delivered an SGA infant. Furthermore, almost half of these SGA infants (47.5%) had a birthweight <3rd centile. Neonatal outcomes were worse for the SGA infants, with 15.1% (n = 21/205) requiring special care nursery compared to 1.5% (n = 1/205) of those AGA at birth. Conclusions: A reassuring ultrasound with EFW ≥10th centile in the late third trimester should not override clinical concerns of impaired fetal growth at term. [ABSTRACT FROM AUTHOR]

Background: Obesity is prevalent in the Australian antenatal population, but there are scarce data on the prevalence and associated outcomes of body mass index (BMI) ≥50 kg/m2. Aims: To examine the prevalence and outcomes for women with BMI ≥50 kg/m2 delivering in a non‐tertiary hospital. Materials and Methods: Retrospective cohort study of women delivering a singleton pregnancy in a non‐tertiary Victorian hospital during 2011–2016. Women >180 kg were excluded as their care was managed in a tertiary centre. Maternal and perinatal outcomes were analysed by BMI group. Statistical analysis was performed using χ2, Kruskal–Wallis and logistic regression with a significance level of 0.05. Results: Of the 18 518 births between 2011 and 2016, 99.4% had a maternal BMI recorded. The prevalence of BMI ≥50 kg/m2 was 0.5%. Highest complication rates were observed among women with BMI ≥50 kg/m2, including gestational diabetes (29%), hypertensive disorders of pregnancy (20%) and caesarean section (48%). Of infants born to women with BMI ≥50 kg/m2, 12% were late‐pre‐term, 23% required special or intensive care and 20% had birth weight ≥4.0 kg. When compared with obese women with BMI 30–49 kg/m2, women with BMI ≥50 kg/m2 were significantly more likely to develop a hypertensive disorder of pregnancy (preeclampsia adjusted odds ratio (aOR) 3.98 (1.93–8.18), pregnancy‐induced hypertension aOR 3.55 (1.79–7.03)) and deliver a late pre‐term infant (aOR 2.45 (1.31–4.58)). Conclusions: The prevalence of severe maternal obesity in our non‐tertiary setting is higher than previous national estimates. Women with BMI ≥50 kg/m2 are an important subgroup of the obese obstetric population who experience high rates of complications and interventions. Health services need to respond to evolving needs of the antenatal population to achieve the best outcomes for mothers and babies. [ABSTRACT FROM AUTHOR]

Placental insufficiency can cause fetal growth restriction and stillbirth. There are no reliable screening tests for placental insufficiency, especially near-term gestation when the risk of stillbirth rises. Here we show a strong association between low circulating plasma serine peptidase inhibitor Kunitz type-1 (SPINT1) concentrations at 36 weeks' gestation and low birthweight, an indicator of placental insufficiency. We generate a 4-tier risk model based on SPINT1 concentrations, where the highest risk tier has approximately a 2-5 fold risk of birthing neonates with birthweights under the 3rd, 5th, 10th and 20th centiles, whereas the lowest risk tier has a 0-0.3 fold risk. Low SPINT1 is associated with antenatal ultrasound and neonatal anthropomorphic indicators of placental insufficiency. We validate the association between low circulating SPINT1 and placental insufficiency in two other cohorts. Low circulating SPINT1 is a marker of placental insufficiency and may identify pregnancies with an elevated risk of stillbirth. There are no reliable tests for placental insufficiency, which can lead to fetal growth restriction and stillbirth. Here the authors demonstrate that low levels of circulating SPINT1 are associated to low birthweight, and several ultrasound and neonatal anthropomorphic indicators of placental insufficiency. [ABSTRACT FROM AUTHOR]

Study Question: What is the frequency of major chromosome abnormalities in a population-based diagnostic data set of genomic tests performed on miscarriage, fetal and infant samples in a state with >73 000 annual births?Summary Answer: The overall frequency of major chromosome abnormalities in the entire cohort was 28.2% (2493/8826), with a significant decrease in the detection of major chromosome abnormalities with later developmental stage, from 50.9% to 21.3% to 15.6% of tests in the miscarriage, prenatal and postnatal cohorts, respectively.What Is Known Already: Over the past decade, technological advances have revolutionized genomic testing at every stage of reproduction. Chromosomal microarrays (CMAs) are now the gold standard of chromosome assessment in prenatal diagnosis and pediatrics.Study Design, Size, Duration: A population-based cohort study including all chromosome analysis was performed in the Australian state of Victoria during a 24-month period from January 2015 to December 2016. All samples obtained via invasive prenatal diagnosis and postnatal samples from pregnancy tissue and infants ≤12 months of age were included.Participants/materials, Setting, Methods: A research collaboration of screening and diagnostic units in the Australian state of Victoria was formed (the Perinatal Record Linkage collaboration), capturing all instances of prenatal and postnatal chromosome testing performed in the state. Victoria has over 73 000 births per annum and a median maternal age of 31.5 years. We analyzed our population-based diagnostic data set for (i) chromosome assessment of miscarriage, prenatal diagnosis and postnatal samples; (ii) testing indications and diagnostic yields for each of these cohorts; (iii) and the combined prenatal/infant prevalence of 22q11.2 deletion syndrome (DS) as a proportion of all births ≥20 weeks gestation.Main Results and the Role Of Chance: During the 24-month study period, a total of 8826 chromosomal analyses were performed on prenatal and postnatal specimens in Victoria. The vast majority (91.2%) of all chromosome analyses were performed with CMA.The overall frequency of major chromosome abnormalities in the entire cohort was 28.2% (2493/8826). There was a significant decreasing trend in the percentage of chromosome abnormalities with later developmental stage from 50.9% to 21.3% to 15.6% in the miscarriage, prenatal and postnatal cohorts, respectively (χ2 trend = 790.0, P < 0.0001). The total frequency of abnormalities in the live infant subgroup was 13.4% (244/1816). The frequencies of pathogenic copy number variants (CNVs) detected via CMA for the miscarriage, prenatal and postnatal cohorts were 1.9% (50/2573), 2.2% (82/3661) and 4.9% (127/2592), respectively. There was a significant increasing trend in the frequency of pathogenic CNVs with later developmental stage (χ2 trend = 39.72, P < 0.0001). For the subgroup of live infants, the pathogenic CNV frequency on CMA analysis was 6.0% (109/1816). There were 38 diagnoses of 22q11.2 DS, including 1 miscarriage, 15 prenatal and 22 postnatal cases. After excluding the miscarriage case and accounting for duplicate testing, the estimated prevalence of 22q11 DS was 1 in 4558 Victorian births.Limitations, Reasons For Caution: Clinical information was missing on 11.6% of postnatal samples, and gestational age was rarely provided on the miscarriage specimens. We were unable to obtain rates of termination of pregnancy and stillbirth in our cohort due to incomplete data provided by clinical referrers. We therefore cannot make conclusions on pregnancy or infant outcome following diagnostic testing. Childhood and adult diagnoses of 22q11 DS were not collected.Wider Implications Of the Findings: Our study marks a complete transition in genomic testing from the G-banded karyotype era, with CMA now established as the first line investigation for pregnancy losses, fetal diagnosis and newborn/infant assessment in a high-income setting. Integration of prenatal and postnatal diagnostic data sets provides important opportunities for estimating the prevalence of clinically important congenital syndromes, such as 22q11 DS.Study Funding/competing Interest(s): L.H. is funded by a National Health and Medical Research Council Early Career Fellowship (1105603); A.L. was funded by a Mercy Perinatal Research Fellowship; J.H. was funded by a National Health and Medical Research Council Senior Research Fellowship (10121252). The funding bodies had no role in the conduct of the research or the manuscript. Discretionary funding from the Murdoch Children's Research Institute has supported the prenatal diagnosis data collection and reporting over the years.Dr Ricardo Palma-Dias reports a commercial relationship with Roche Diagnostics, personal fees from Philips Ultrasound, outside the submitted work. Debbie Nisbet reports a commercial relationship with Roche Diagnostics, outside the submitted work.Trial Registration Number: NA. [ABSTRACT FROM AUTHOR]

Objective To evaluate the implementation of the 2013 Royal Australian and New Zealand College of Obstetricians and Gynaecologists ‘Management of Hepatitis B in Pregnancy’ guideline. Methods Retrospective cohort study of the clinical management and obstetric outcomes among hepatitis B virus-positive women in a single tertiary maternity hospital. Women with viral load >200,000 IU/ml were referred to a specialised clinic for consideration of tenofovir disoproxil fumarate therapy to reduce mother to child transmission. Results A total of 11,496 women gave birth during the study period, of which 101 (0.9%) women were hepatitis B virus positive. Viral load was measured in 99 (98%) of 101 hepatitis B virus-positive women; 30 (30%) had a viral load >200,000 IU/ml. Twenty-six women accepted tenofovir disoproxil fumarate; of these, 23 had a successful virological response (viral load <200,000 IU/ml before delivery). Conclusions Adherence to updated management guidelines and patient acceptance of tenofovir disoproxil fumarate in our Australian population were high when provided in the context of a dedicated perinatal service. [ABSTRACT FROM AUTHOR]

Noninvasive prenatal DNA testing is the vanguard of genomic medicine. In only four years, this screening test has revolutionized prenatal care globally and opened up new prospects for personalized medicine for the fetus. There are widespread implications for increasing the scope of human genetic variation that can be detected before birth, and for discovering more about maternofetal and placental biology. These include an urgent need to develop pretest education for all pregnant women and consistent post-test management recommendations for those with discordant test results. The reduction in invasive testing has had downstream effects on specialist training and caused many countries to re-examine their national approaches to prenatal screening. Finally, the accumulating datasets of genomic information on pregnant women and their fetuses raise ethical issues regarding consent for future data mining and intellectual property. [ABSTRACT FROM AUTHOR]

The health services participating in the CoMaND and CHOPAN projects include: Mercy Health (Mercy Hospital for Women, Werribee Mercy Hospital); the Royal Women's Hospital, the Women's at Sandringham; Monash Health (Monash Medical Centre, Casey Hospital, Dandenong Hospital); Northern Health (the Northern Hospital); Western Health (Joan Kirner Women's and Children's Hospital); Eastern Health (Box Hill Hospital, the Angliss Hospital); Peninsula Health (Frankston Hospital). Keywords: COVID-19; Maternal health; Perinatal; Obstetrics; Pregnancy; Neonatology; Clinical trials as topic EN COVID-19 Maternal health Perinatal Obstetrics Pregnancy Neonatology Clinical trials as topic 433 434 2 11/02/21 20211101 NES 211101 Acknowledgements The CoMaND project is funded by a philanthropic grant from the Norman Beischer Medical Research Foundation and a University of Melbourne Department of Obstetrics and Gynaecology Innovation grant. Neonatology, COVID-19, Maternal health, Perinatal, Obstetrics, Pregnancy, Clinical trials as topic. [Extracted from the article]

Background: Although specialised clinics for multiple pregnancies are recommended by several Obstetrics and Gynaecology governing bodies, studies examining outcome before and after introduction of such clinics remain few, were performed predominantly in North America in the 1990s, and either amongst dichorionic twin pregnancies only or where chorionicity was not specified. Our objective, in the modern setting with twins of known chorionicity, was to compare maternal and neonatal outcomes of twin pregnancies before and after commencement of a consultant-led, multidisciplinary twins clinic (TC).Methods: Retrospective cohort study of 513 women, with birth of twins at ≥20 weeks' gestation, January 2007 to November 2011, at a metropolitan tertiary maternity hospital, Sydney, Australia. Demographic, pregnancy, and outcome data were obtained from hospital databases. Women receiving TC care (2009-2011) were compared to those receiving general antenatal clinic (ANC) care (2007-2010) and private care (2009-2011). Other models of care were excluded. Main outcome measures were total maternal inpatient stay, mode of birth, gestational age at birth, and neonatal nursery admission.Results: 286 women were included in the main analyses: 84 attended ANC, 101 TC, and 101 a private obstetrician. TC women had similar demographics to ANC women and were slightly younger than private patients. TC women had lower Caesarean section rates (55% vs. 70% ANC and 76% private, p = 0.008) and fewer late preterm (34 + 0-36 + 6 weeks) births, (26%TC vs. 44% ANC and 41% private, p < 0.001). Median maternal inpatient stay was shorter in TC than ANC (7 vs. 8 days, p = 0.009) and similar to private (7 days). Nursery admission rates were higher in private patients (67% vs. 49% ANC and 47% TC, p = 0.001) and average birthweight lower (2283 g vs. 2501 g ANC and 2496 g TC, p < 0.001).Conclusions: Within a single centre, maternal and neonatal twin pregnancy outcomes varied significantly by model of care. Introducing a specialised twins clinic in our setting decreased Caesarean section rates, late preterm birth, and inpatient stay compared to ANC. [ABSTRACT FROM AUTHOR]

Background: It is not known whether fasting affects levels of circulating placenta-specific transcripts.Objective: To assess whether a glucose load affects circulating placenta-specific transcripts.Method: RNA was extracted from paired blood samples (fasting and 1-h post 75 g oral glucose) from 22 women. Placenta-specific genes were measured by RT-qPCR.Results: There was no change in ADM, CSH1, PAPPA2, PSG1 or TAC3 expression between fasting and post-glucose states. However, HTRA1 decreased after glucose load.Conclusion: Maternal fasting state does not influence expression of the majority of placenta-specific genes but may need to be accounted for when validating biomarkers of placental disease. [ABSTRACT FROM AUTHOR]

Background Nearly two decades ago, the discovery of circulating cell-free fetal DNA in maternal blood created a paradigm shift in prenatal testing. Recent advances in DNA sequencing technology have facilitated the rapid translation of DNA-based testing into clinical antenatal care. Content In this review, we summarize the technical approaches and current clinical applications of noninvasive testing using cell-free DNA in maternal plasma. We discuss the impact of these tests on clinical care, outline proposed integration models, and suggest future directions for the field. Summary The use of cell-free DNA in maternal blood for the detection of fetal rhesus D antigen status, fetal sex, and common whole chromosomal aneuploidies is now well established, although testing for aneuploidy is still considered screening and not diagnostic. Further advances in technology and bioinformatics may see future clinical applications extend to the noninvasive detection of fetal subchromosomal aneuploidy, single gene disorders, and the entire fetal genome. [ABSTRACT FROM AUTHOR]

Objective: One in three pregnant women in the United States is obese. Their offspring are at increased risk for neurodevelopmental and metabolic morbidity. Underlying molecular mechanisms are poorly understood. We performed a global gene expression analysis of mid-trimester amniotic fluid cell-free fetal RNA in obese versus lean pregnant women. Methods: This prospective pilot study included eight obese (BMI≥30) and eight lean (BMI<25) women undergoing clinically indicated mid-trimester genetic amniocentesis. Subjects were matched for gestational age and fetal sex. Fetuses with abnormal karyotype or structural anomalies were excluded. Cell-free fetal RNA was extracted from amniotic fluid and hybridized to whole genome expression arrays. Genes significantly differentially regulated in 8/8 obese-lean pairs were identified using paired t-tests with the Benjamini-Hochberg correction (false discovery rate of <0.05). Biological interpretation was performed with Ingenuity Pathway Analysis and the BioGPS gene expression atlas. Results: In fetuses of obese pregnant women, 205 genes were significantly differentially regulated. Apolipoprotein D, a gene highly expressed in the central nervous system and integral to lipid regulation, was the most up-regulated gene (9-fold). Apoptotic cell death was significantly down-regulated, particularly within nervous system pathways involving the cerebral cortex. Activation of the transcriptional regulators estrogen receptor, FOS, and STAT3 was predicted in fetuses of obese women, suggesting a pro-estrogenic, pro-inflammatory milieu. Conclusion: Maternal obesity affects fetal neurodevelopmental and metabolic gene expression as early as the second trimester. These findings may have implications for postnatal neurodevelopmental and metabolic abnormalities described in the offspring of obese women. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify the tissue expression patterns and biological pathways enriched in term amniotic fluid cell-free fetal RNA by comparing functional genomic analyses of term and second-trimester amniotic fluid supernatants. METHODS: This was a prospective whole genome micro-array study comparing eight amniotic fluid samples collected from women at term who underwent prelabor cesarean delivery and eight second-trimester amniotic fluid samples from routine amniocenteses. A functional annotation tool was used to compare tissue expression patterns in term and second-trimester samples. Pathways analysis software identified physiologic systems, molecular and cellular functions, and upstream regulators that were significantly overrepresented in term amniotic fluid. RESULTS: There were 2,871 significantly differentially regulated genes. In term amniotic fluid, tissue expression analysis showed enrichment of salivary gland, tracheal, and renal transcripts as compared with brain and embryonic neural cells in the second trimester. Functional analysis of genes upregulated at term revealed pathways that were highly specific for postnatal adaptation such as immune function, digestion, respiration, carbohydrate metabolism, and adipogenesis. Inflammation and prostaglandin synthesis, two key processes involved in normal labor, were also activated in term amniotic fluid. CONCLUSIONS: Transcriptomic analysis of amniotic fluid cell-free fetal RNA detects fetal maturation processes activated in term pregnancy. These findings further develop the concept of amniotic fluid supernatant as a real-time gene expression "summary fluid" and support its potential for future studies of fetal development. [ABSTRACT FROM AUTHOR]