General Obstetric Population Research Articles

Strategies to minimize false positives and interpret novel microdeletions based on maternal copy-number variants in 87,000 noninvasive prenatal screens

BackgroundNoninvasive prenatal screening (NIPS) of common aneuploidies using cell-free DNA from maternal plasma is part of routine prenatal care and is widely used in both high-risk and low-risk patient populations. High specificity is needed for clinically acceptable positive predictive values. Maternal copy-number variants (mCNVs) have been reported as a source of false-positive aneuploidy results that compromises specificity.MethodsWe surveyed the mCNV landscape in 87,255 patients undergoing NIPS. We evaluated both previously reported and novel algorithmic strategies for mitigating the effects of mCNVs on the screen’s specificity. Further, we analyzed the frequency, length, and positional distribution of CNVs in our large dataset to investigate the curation of novel fetal microdeletions, which can be identified by NIPS but are challenging to interpret clinically.ResultsmCNVs are common, with 65% of expecting mothers harboring an autosomal CNV spanning more than 200 kb, underscoring the need for robust NIPS analysis strategies. By analyzing empirical and simulated data, we found that general, outlier-robust strategies reduce the rate of mCNV-caused false positives but not as appreciably as algorithms specifically designed to account for mCNVs. We demonstrate that large-scale tabulation of CNVs identified via routine NIPS could be clinically useful: together with the gene density of a putative microdeletion region, we show that the region’s relative tolerance to duplications versus deletions may aid the interpretation of microdeletion pathogenicity.ConclusionsOur study thoroughly investigates a common source of NIPS false positives and demonstrates how to bypass its corrupting effects. Our findings offer insight into the interpretation of NIPS results and inform the design of NIPS algorithms suitable for use in screening in the general obstetric population.

Impact of prenatal exercise on maternal harms, labour and delivery outcomes: a systematic review and meta-analysis.

To perform a systematic review of the relationships between prenatal exercise and maternal harms including labour/delivery outcomes. Systematic review with random effects meta-analysis and meta-regression. Online databases were searched up to 6 January 2017. Studies of all designs were included (except case studies) if they were published in English, Spanish or French and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise, alone ["exercise-only"] or in combination with other intervention components [e.g., dietary; "exercise + co-intervention"]) and outcome (preterm/prelabour rupture of membranes, caesarean section, instrumental delivery, induction of labour, length of labour, vaginal tears, fatigue, injury, musculoskeletal trauma, maternal harms (author defined) and diastasis recti). 113 studies (n=52 858 women) were included. 'Moderate' quality evidence from exercise-only randomised controlled trials (RCTs) indicated a 24% reduction in the odds of instrumental delivery in women who exercised compared with women who did not (20 RCTs, n=3819; OR 0.76, 95% CI 0.63 to 0.92, I 2= 0 %). The remaining outcomes were not associated with exercise. Results from meta-regression did not identify a dose-response relationship between frequency, intensity, duration or volume of exercise and labour and delivery outcomes. Prenatal exercise reduced the odds of instrumental delivery in the general obstetrical population. There was no relationship between prenatal exercise and preterm/prelabour rupture of membranes, caesarean section, induction of labour, length of labour, vaginal tears, fatigue, injury, musculoskeletal trauma, maternal harms and diastasis recti.

Antiphospholipid Antibodies in a General Obstetric Population: Clinical Impact on Pregnancy Outcome and Relationship with the M2 Haplotype in the Annexin A5 (ANXA5) Gene.

Antiphospholipid (aPL) antibodies are recognised risk factors for adverse obstetric outcomes. Recently, carriers of the M2 haplotype in the Annexin A5 gene have been shown to have a higher susceptibility to develop aPL antibodies. In a general obstetric population, we prospectively evaluated the possible relationship between: (1) aPL antibodies and M2 haplotype; and (2) aPL antibodies and/or M2 haplotype and obstetric outcomes. From a cohort of 3,097 consecutive pregnant women, 1,286 samples were analysed for the presence of both anti-cardiolipin and anti-human β2-glycoprotein I antibodies; samples with available DNA (n = 606) were also investigated for the M2 haplotype. Overall, 41/1,286 (3.2%) women showed the presence of aPL antibodies. Among them, 2 (4.8%) experienced a pregnancy loss and 38 (92.7%) gave birth to live-born babies (p-value = non-significant vs. those without aPL antibodies). M2 haplotype was identified in 140 (23.1%) out of 606 women with DNA available: 3/140 (2.1%) M2 carriers and 17/466 (3.6%) non-carriers tested positive for aPL antibodies, respectively (p-value = non-significant). In total, 15/150 (10%) M2 and/or aPL antibody carriers, and 38/445 (8.5%) non-aPL antibody and/or M2 carriers suffered from obstetric complications, respectively (p-value = non-significant). No relationship between aPL antibodies and M2 haplotype was found. Furthermore, neither aPL antibodies nor the M2 haplotype is associated with obstetric complications.

Preterm erken membran rüptürü durumunda umbilikal kord prolapsusu: Ne zaman daha dikkatli olmalı

Purpose: To describe the umbilical cord prolapse rates in patients with preterm premature rupture of membranes (PPROM) between 24 weeks and 33 weeks and 6 days gestation and to define the associated factors with umbilical cord prolapse.Material and methods: Patients admitted due to PPROM between 24 weeks and 33 weeks and 6 days of gestation, and followed in clinic are included in the study. Primary aim of the study was to describe the umbilical cord prolapse rates. Secondary aim was to describe the pregnancy specific factors associated with umbilical cord prolapse.Results: Total 88 patients are included in the study. Umbilical cord prolapse rate was 3.4% (3/88). Umbilical cord prolapses, all occurred in the first week after membrane rupture. All were multiparas and at non-vertex presentation. Conclusion: Umbilical cord prolapse is much frequent after PPROM compared to general obstetric population. Clinicians should be more cautious in follow-up of patients after PPROM in case of earlier gestational weeks, transverse situs and non-vertex presentations, especially in the first week after PPROM.

Chronic Hypertension in Pregnancy: New Concepts for Classification and Management.

Chronic hypertension in pregnancy is traditionally classified according to degree of blood pressure (BP) elevation. Alternatively, stratifying women as high or low risk based on the etiology of hypertension, baseline work-up, and comorbid medical conditions will better inform clinicians about thresholds to initiate antihypertensive therapy, target BPs, frequency of antepartum visits, and timing of delivery. Women classified as high-risk chronic hypertension as described here require stricter BP management and more frequent follow-up visits as their associated rates of adverse maternal and/or fetal/neonatal outcomes appear higher than women classified as low-risk chronic hypertension. The latter group can in most cases be managed similarly to the general obstetric population.

Genetic Counselors' Perspectives About Cell-Free DNA: Experiences, Challenges, and Expectations for Obstetricians.

The expansion of cell-free fetal DNA (cfDNA) screening for a larger and diverse set of genetic variants, in addition for use among the low-risk obstetric population, presents important clinical challenges for all healthcare providers involved in the delivery of prenatal care. It is unclear how to leverage the different members of the healthcare team to respond to these challenges. We conducted interviews with 25 prenatal genetic counselors to understand their experience with the continued expansion of cfDNA screening. Participants supported the use of cfDNA screening for the common autosomal aneuploidies, but noted some reservations for its use to identify fetal sex and microdeletions. Participants reported several barriers to ensuring that patients have the information and support to make informed decisions about using cfDNA to screen for these different conditions. This was seen as a dual-sided problem, and necessitated additional education interventions that addressed patients seeking cfDNA screening, and obstetricians who introduce the concepts of genetic risk and cfDNA to patients. In addition, participants noted that they have a professional responsibility to educate obstetricians about cfDNA so they can be prepared to be gatekeepers of counseling and education about this screening option for use among the general obstetric population.

Unintended hysterotomy extension during caesarean delivery: risk factors and maternal morbidity

We conducted an observational retrospective cohort study to evaluate the risk factors and the maternal morbidity associated with unintended extensions of the hysterotomy during caesarean delivery. We evaluated 2707 women who underwent low-transverse caesarean deliveries in 2011 at an academic, tertiary-care hospital. Hysterotomy extensions were identified through operative reports. Of the 2707 caesarean deliveries, 392 (14.5%) had an unintended hysterotomy extension. On the multivariable regression modelling, neonatal weight (OR 1.42; 95%CI 1.17–1.73), the arrest of labour [first-stage arrest (2.42; 1.73–3.38); second-stage arrest (5.54; 3.88–7.90)] and a non-reassuring foetal status (1.65; 1.20–2.25) were significantly associated with hysterotomy extensions. Hysterotomy extensions were significantly associated with an increased morbidity including an estimated blood loss >1200 millilitres (2.06; 1.41–3.02), a decline in postoperative haemoglobin ≥3.7 g/dL (2.07; 1.35–3.17), an evaluation for lower urinary tract injury (5.58; 3.17–9.81), and a longer operative time (8.11; 6.33–9.88). Based on these results, we conclude that unintended hysterotomy extensions significantly increase the maternal morbidity of caesarean deliveries.Impact statementWhat is already known on this subject? Maternal morbidity associated with caesarean delivery (CD) is significantly greater than that in vaginal delivery. Unintended extensions of the hysterotomy occur in approximately 4–8% of CDs and are more common after a prolonged second stage of labour. The morbidity associated with hysterotomy extensions has been incompletely evaluated.What do the results of this study add? We demonstrate a rate of hysterotomy extension in a general obstetric population of approximately 15%, which is higher than previously reported estimates, and represents a potential doubling of the rate of the unintended hysterotomy extensions in recent years. The most significant risk factor for a hysterotomy extension was a second-stage labour arrest with a fourfold increase in the frequency of extensions. A hysterotomy extension is a significant independent risk factor for an intraoperative haemorrhage, a drop in postoperative haemoglobin, an intraoperative evaluation for lower urinary tract injury, and longer CD operative times.What are the implications of these findings for clinical practice and/or further research? A second-stage arrest is a strong independent risk factor for a hysterotomy extension. Recent re-evaluations of the labour curve that extend the second stage of labour will likely increase the frequency of CDs performed after a prolonged second stage. In these scenarios, obstetricians should be prepared for an unintended hysterotomy extension and for the possibility of a longer procedure with the increased risks of blood loss and the need for evaluation of the lower urinary tract.

A Paradigm Shift: Considerations in Prenatal Cell-Free DNA Screening.

Testing to determine the health of a fetus has undergone multiple iterations since the widespread adoption of amniocentesis in the 1970s, including several combinations of ultrasound and/or maternal serum screening. The clinical paradigm for prenatal screening for fetal chromosome aneuploidies was transformed by the introduction of cell-free DNA (cfDNA) screening or noninvasive prenatal screening in 2011. The clinical performance of cfDNA screening is well-established for the most common autosomal and sex chromosome aneuploidies with a detection rate exceeding 90% for all aneuploidies. One of the most significant advantages of cfDNA screening relative to maternal serum screening is the markedly reduced false-positive rate, which is <0.5%. The clinical implementation of cfDNA screening is discussed at length, including key biological, preanalytical, and analytical factors that affect test performance. cfDNA prenatal screening for whole chromosome aneuploidies has become routine in high-risk obstetric populations. There is tremendous interest in expanding cfDNA screening to the general obstetric population. Early studies suggest that routine application of cfDNA screening is both feasible and effective, although significant economic and quality control considerations remain.

Cell-free fetal DNA testing in singleton IVF conceptions.

Are fetal fraction, test failure rate and positive predictive value (PPV) of cell-free fetal DNA (cffDNA) testing different in singleton IVF conceptions compared to spontaneous conceptions? Fetal fraction is significantly lower; test failure rate is higher and PPV of cffDNA testing is lower in singleton pregnancies conceived by IVF than those conceived spontaneously. cffDNA testing, which analyses circulating cffDNA in maternal blood, has very high accuracy for detection of trisomy 21 in the general obstetric population. Focused and conclusive evidence regarding the test characteristics of cffDNA testing in IVF conceived pregnancies is lacking. This was a retrospective cohort study including spontaneously and IVF conceived singleton pregnancies collected consecutively between April 2013 and November 2016. A total of 4633 spontaneously conceived and 992 IVF pregnancies were included. The study was performed at an obstetric and gynecological ultrasound clinic in Melbourne, Australia. Participants had screening for trisomies 21, 18 and 13, as well as sex chromosome aneuploidies (SCA) performed with cffDNA testing after 10 weeks' gestation. Multivariate regression analysis was used to determine significant predictors of logarithmically transformed fetal fraction and test failure. Comparison of test characteristics between study groups was performed adopting a significance level of 5%. Median fetal fraction was lower (10.3% [interquartile range (IQR), 7.7-13.5] versus 11.9% [IQR, 9.1-15.0]; P = 0.005), test failure rate was higher (5.2 versus 2.2%; P < 0.001) and positive predictive value (PPV) for trisomies 18, 13 and SCA was poorer in IVF pregnancies compared to those spontaneously conceived. Multivariate linear regression analysis demonstrated that IVF conception, increased BMI, earlier gestational age and South and East Asian ethnicities were independent predictors of lower fetal fraction. Multiple logistic regression analysis found IVF conception and increased BMI to be independently associated with test failure. PPV was high for trisomy 21 in IVF conception (100.0%), but was lower for other trisomies when compared with the non-IVF population. IVF details were unascertainable for 210 cases, as the information was not available through our data collection points. Inability to karyotype some cases at high-risk for SCA, due to patients' choice, and the occurrence of miscarriages and terminations, resulted in the exclusion of high-risk cases when calculating PPV. Pregnancy outcomes were not available in low-risk pregnancies and negative predictive values could not be calculated. The limitations revealed by this work should be taken into account during pre-test counseling in pregnant women who conceive by IVF. No external source of financial support was provided for this research. The authors report no conflicts of interest.

Mortalité maternelle par hémorragie, résultats de l’ENCMM, France 2010–2012

Haemorrhage is the first cause of maternal mortality and morbidity in France and a quality of care marker. Haemorrhage rate in France is around 5 to 10% of deliveries. PPH is defined as a post-partum blood loss≥500mL whatever the delivery route and sometime blood can be concealed inside the pelvis. Between 2010 and 2012 in France, 29 deaths were related to haemorrhage giving a maternal mortality ratio of 1,2/100,000 live births (CI 95% 0,8–1,7). Haemorrhage cases decreased from last triennium (2007–2009) especially for uterine atony cases (12/29) but remains the first leading cause of direct maternal death. Patients with previous cesarean birth were more represented than in general obstetrical population (11/23). Substandard care were mainly due to delays in diagnosis of hemoperitoneum, delays in adequate resuscitation because of reassuring vital signs (normal blood pressure or normal hematocrite at the initial stage of bleeding) or organisational mistakes.

The Relationship Between 2009 Pandemic H1N1 Influenza During Pregnancy and Preterm Birth: A Population-based Cohort Study.

Previous studies of maternal influenza illness and preterm birth have yielded inconsistent results. Our objective was to assess the association between 2009 pandemic H1N1 (pH1N1) influenza during pregnancy and preterm birth in a large obstetrical population. We linked a province-wide birth registry with health administrative databases to identify influenza-coded hospitalizations, emergency department visits, or physician visits among pregnant women during the 2009 H1N1 pandemic (our proxy for clinical pH1N1 influenza illness). Using Cox regression, we estimated adjusted hazard ratios (aHR) for preterm birth and spontaneous preterm birth treating influenza as a time-varying exposure. Among 192,082 women with a singleton live birth, 2,925 (1.5%) had an influenza-coded health care encounter during the 2009 H1N1 pandemic. Compared with unexposed pregnancy time, there was no association between exposure to the pandemic, with or without clinical influenza illness, and preterm birth (no pH1N1 diagnosis: aHR = 1.0; 95% confidence interval [CI] = 0.98, 1.1; pH1N1 diagnosis: aHR = 1.0; 95% CI = 0.88, 1.2). Among women with preexisting medical conditions, influenza was associated with increased preterm birth (aHR = 1.5; 95% CI = 1.1, 2.2) and spontaneous preterm birth (aHR = 1.7; 95% CI = 1.1, 2.6), and these associations were strongest in the third trimester and when data were analyzed to allow for a transient acute effect of influenza. In the general obstetrical population, there was no association between pH1N1 influenza illness and preterm birth, but women with preexisting medical conditions known to increase the risk of influenza-associated morbidity were at elevated risk.

Implications of failure to achieve a result from prenatal maternal serum cell-free DNA testing: a historical cohort study.

To investigate the pregnancy outcomes in a cohort of women who failed to obtain a result in non-invasive prenatal testing (NIPT). Historical cohort study. A multicentre private practice in Sydney, Australia. Women who failed to obtain a result from NIPT (n = 131). The maternal characteristics, antenatal investigations and pregnancy outcomes for these women were compared with those who obtained a result at the same practice and to the general Australian obstetric population. Antenatal investigations: pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotrophin (β-hCG), placental growth factor (PlGF), uterine artery pulsatility index (PI), mean arterial pressure (MAP). Pregnancy outcomes: chromosomal abnormality, pre-eclampsia, gestational diabetes, small-for-gestational-age (SGA), preterm delivery. Only 1.1% of NIPT samples failed to return a result. This cohort was significantly older and had significantly increased weight compared with the general Australian obstetric population. Pregnancy outcomes were available for 94% of the cohort. There were significantly higher rates of chromosomal aneuploidies (6.5% versus 0.2%, P < 0.0001), pre-eclampsia (11% versus 1.5%, P < 0.0001) and gestational diabetes (23% versus 7.5%, P < 0.0001) compared with the general obstetric population. Rates of preterm delivery and SGA were elevated but did not reach significance. Antenatal investigations demonstrated decreased PAPP-A MoM (0.75 versus 1.14, P < 0.0001), decreased free β-hCG (0.71 versus 1.01, P < 0.0001) and increased uterine artery PI (1.79 versus 1.65, P = 0.02). Women who fail to obtain a result from NIPT are at increased risk of adverse pregnancy outcomes, in particular chromosomal aneuploidy, gestational diabetes and pre-eclampsia. None received. Women who fail to obtain a result from cell-free DNA NIPT are at increased risk of adverse pregnancy outcomes.

Extracellular vesicles yield predictive pre-eclampsia biomarkers

ABSTRACTCirculating extracellular vesicles (EVs) such as cholera toxin B chain (CTB)- or annexin V (AV)-binding EVs were previously shown to be rich sources of biomarkers. Here we test if previously identified pre-eclampsia (PE) candidate biomarkers, TIMP-1 in CTB-EVs (CTB-TIMP) and PAI-1 in AV-EVs (AV-PAI) complement plasma PlGF in predicting PE in a low-risk obstetric population. Eight hundred and forty-three prospectively banked plasma samples collected at 28 + 0 to 32 + 0 gestation weeks in the Neonatal and Obstetrics Risk Assessment (NORA) cohort study were assayed by sandwich ELISAs for plasma PlGF, CTB-TIMP1 and AV-PAI1. Nineteen patients subsequently developed PE 7.3 (±2.9) weeks later at a mean gestational age of 36.1 ± 3.5 weeks. The biomarkers were assessed for their predictive accuracy for PE using stepwise multivariate logistic regression analysis with Firth correction and Areas under the curve (AUC). To achieve 100% sensitivity in predicting PE, the cut-off for plasma PlGF, CTB-TIMP1 & AV-PAI1 were set at <1235, ≤300 or >1300 and <10,550 pg/mL plasma, respectively. The corresponding AUCs, specificity and PPV at a 95% confidence interval were 0.92, 52.1% and 4.7%; 0.72, 44.5% and 4.0%; and 0.69, 21.5% and 2.9%, respectively. At 100% sensitivity, the three biomarkers had a combined AUC of 0.96, specificity of 78.6%, and PPV of 9.9%.This is the first large cohort validation of the utility of EV-associated analytes as disease biomarkers. Specifically, EV biomarkers enhanced the predictive robustness of an existing PE biomarker sufficiently to justify PE screening in a low-risk general obstetric population.

Pregnancy outcomes in adult patients with dermatomyositis and polymyositis.

The idiopathic inflammatory myopathies dermatomyositis (DM) and polymyositis (PM) are autoimmune diseases that can affect females of childbearing potential. We assessed pregnancy outcomes in DM and PM patients compared with the general obstetric population. The Nationwide Inpatient Sample (NIS) (1993-2007) was used to identify delivery-associated hospitalizations in women with DM or PM (DM/PM, n = 853). Controls were from the general obstetric population delivery-associated hospitalizations matched to each case by year of delivery. Pregnancy outcomes included hospital length of stay (LOS), hypertensive disorders (HTN), premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), and cesarean delivery. Multivariate regression analyses were performed using maternal age, race/ethnicity, and diabetes mellitus as covariates. On multivariate analysis, patients with DM/PM had longer LOS compared to controls (p < 0.001). DM/PM was associated with an increased risk of hypertensive disorders compared to controls (OR = 2.90, 95% CI: 2.00-4.22). There were no differences in rates of PROM, IUGR, or cesarean section in patients with DM/PM compared with controls. Independent of a DM/PM diagnosis, African-American race, older age, and diagnosis of diabetes increased the hospital LOS (p < 0.001). African-American race and diabetes increased the risk of hypertensive disorders (OR = 1.38, 95% CI: 1.19-1.60; OR = 2.94, 95% CI: 2.04-4.23, respectively) compared to controls. These data suggest that patients with inflammatory myopathies are at increased risk of hypertensive disorders of pregnancy and longer length of hospitalization. Vigilant monitoring of blood pressure is advisable in pregnant patients with DM or PM.

Mortalité maternelle par hémorragie, résultats de l’ENCMM, France 2010–2012

Haemorrhage is the first cause of maternal mortality and morbidity in France and a quality of care marker. Haemorrhage rate in France is around 5 to 10% of deliveries. PPH is defined as a post-partum blood loss≥500mL whatever the delivery route and sometime blood can be concealed inside the pelvis. Between 2010 and 2012 in France, 29 deaths were related to haemorrhage giving a maternal mortality ratio of 1.2/100,000 live births (CI 95% 0.8–1.7). Haemorrhage cases decreased from last triennium (2007–2009) especially for uterine atony cases (12/29) but remains the first leading cause of direct maternal death. Patients with previous cesarean birth were more represented than in general obstetrical population (11/23). Substandard care were mainly due to delays in diagnosis of hemoperitoneum, delays in adequate resuscitation because of reassuring vital signs (normal blood pressure or normal hematocrite at the initial stage of bleeding) or organisational mistakes.

Challenges of Anticoagulation Therapy in Pregnancy.

Thrombotic complications in pregnancy represent a major cause of morbidity and mortality. Pregnancy is a primary hypercoagulable state due to enhanced production of clotting factors, a decrease in protein S activity, and inhibition of fibrinolysis. These physiologic changes will yield a collective rate of venous thromboembolism (VTE) of about 1-2 in 1000 pregnancies for the general obstetric population, which represents a five- to tenfold increased risk in pregnancy compared to age-matched non-pregnant peers. A select group of women, however, will carry a significantly higher rate of thrombosis due to primary thrombophilia, either inherited or acquired. This introduces a population of women who may benefit from prophylactic anticoagulation, either antepartum or postpartum. The coagulation changes that occur in preparation for the hemostatic challenges of delivery endure for several weeks postpartum. In fact, daily risk for pulmonary embolism (PE) is the highest postpartum. Use of anticoagulation in pregnancy introduces particular risk at the time of delivery, where bleeding and clotting risk collide. Altered metabolism rates of anticoagulants in pregnant women often necessitate closer monitoring than is required outside of pregnancy in order to ensure efficacy and safety. Heparin products are the mainstay of treating VTE in pregnancy, chiefly because they do not cross the placenta. In women with mechanical heart valves, the ideal anticoagulation regimen remains controversial as heparin use has shown inferior outcomes for preventing thromboembolic complications compared to warfarin, but warfarin carries risk for fetal embryopathy. Other populations where a heparin alternative is necessary include women with a history of heparin-associated thrombocytopenia (HIT) or other heparin intolerance. Further challenging the management of anticoagulation in pregnancy is the dearth of randomized clinical trials. The evidence governing treatment recommendations is largely based on expert guidelines, observational studies, or extrapolation from non-pregnant cohorts. A careful critique of a woman's history, as well as the available data, is essential for optimal management of anticoagulation in pregnancy. Such decisions should involve a multidisciplinary team involving obstetrics, hematology, cardiology, and anesthesia.

Maternal hyperglycemia in singleton pregnancies conceived by IVF may be modified by first-trimester BMI.

STUDY QUESTIONDoes IVF independently increase the risk of gestational diabetes mellitus (GDM) and is this increase in risk modified by maternal body mass index?SUMMARY ANSWERIVF appears to be an independent risk factor for GDM and elevated blood glucose levels in overweight women (BMI > 25 kg/m2).WHAT IS KNOWN ALREADYIVF has been associated with increased risk of GDM, but most previous studies did not adequately assess confounding or effect modification by other risk factors.STUDY DESIGN, SIZE, DURATIONCross-sectional study using data from 1089 women with singleton pregnancies who participated in a Singaporean birth cohort study (GUSTO) and received a 75 g oral glucose tolerance test (OGTT) at 26–28 weeks gestation.PARTICIPANTS/MATERIALS, SETTING, METHODSA total of 1089 women (n = 1013 conceived spontaneously, n = 76 conceived through IVF) with singleton pregnancies received a 75 g OGTT at 26–28 weeks gestation. Fasting and 2 h postprandial blood glucose levels were assayed. World Health Organization criteria (1999) standard criteria were used to classify GDM: ≥7.0 mmol/L for fasting and/or ≥7.8 mmol/L for 2-h postprandial plasma glucose levels, which was the clinical guideline in use during the study.MAIN RESULTS AND THE ROLE OF CHANCEIVF pregnancies had nearly double the odds of GDM (OR = 1.83, 95% CI: 1.03–3.26) and elevated fasting (mean difference = 0.12 mmol/L, 95% CI: 0.00–0.24) and OGTT 2-h blood glucose levels (mean difference = 0.64 mmol/L, 95% CI: 0.27–1.01), after adjusting for commonly recognized risk factors for GDM. After stratification by first-trimester BMI, these increased risks of GDM (OR = 3.54, 95% CI: 1.44–8.72) and elevated fasting (mean difference = 0.39 mmol/L, 95% CI: 0.13–0.65) and 2-h blood (mean difference = 1.24 mmol/L, 95% CI: 0.56–1.91) glucose levels were significant only in the IVF group who is also overweight or obese (BMI > 25 kg/m2).LIMITATIONS REASONS FOR CAUTIONOne limitation of our study is the absence of a 1 h post-OGTT plasma glucose sample, as we were using the 1999 WHO diagnostic criteria (the clinical guideline in Singapore) at the time of our study, instead of the revised 2013 WHO diagnostic criteria. Our cohort may not be representative of the general Singapore obstetric population, although participants were recruited from the two largest maternity hospitals in the country and include both private and subsidized patients.WIDER IMPLICATIONS OF THE FINDINGSIVF appears to be an independent risk factor for GDM and elevated blood glucose levels in overweight women. Our findings reinforce the need to advise overweight or obese women contemplating IVF to lose weight before the procedure to reduce their risk of GDM and hyperglycemia-related adverse outcomes arising therefrom. In settings where universal GDM screening is not routine, overweight or obese women who conceive by IVF should be screened.STUDY FUNDING/COMPETING INTEREST(S)This research was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Program and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC), Singapore (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding was provided by the Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR). K.M.G. and Y.S.C. have received lecture fees from Nestle Nutrition Institute and Danone, respectively. K.M.G., Y.S.C. and S.Y.C. are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. The other authors have nothing to disclose. The other authors have nothing to disclose.TRIAL REGISTRATION NUMBERN/A.

Postnatal Hospital Utilization Among U.S. Women With Intellectual and Developmental Disabilities [10N

INTRODUCTION: Women with intellectual and developmental disabilities (IDD) are at high risk for pregnancy and delivery related complications. However, there are no population-based studies about postnatal hospital utilization among U.S. women with IDD. We sought to examine the risk of postnatal hospital utilization and emergency department (ED) visits among women with and without IDD. METHODS: We conducted population-based retrospective cohort study using the 2002-09 Massachusetts Pregnancy to Early Life Longitudinal data and identified women with (N=541) and without IDD (N=1,623). The primary outcome measures were postnatal hospitalization and ED visits during the one-year postnatal period. RESULTS: Women with IDD have significantly higher risk of hospitalization and emergency department visit than the general obstetric population during the one-year postnatal period. Namely, women with IDD have 3.4 times higher odds (OR; 95% CI, 2.61–4.40; p &lt; 0.001) of being hospitalized and 2.3 times higher odds (OR; 95% CI, 1.82–2.87; p &lt; 0.001) of being admitted to emergency department during the one-year postnatal period compared to the general obstetric population. CONCLUSION: The findings of the study add to the emerging body of research on postnatal hospitalizations among women with IDD. Development, testing and implementation of evidence-based interventions that effectively support women with IDD during their postnatal period are critical. Furthermore, there is critical need for future research to develop postnatal care guidelines for women with IDD, understand the underlying mechanisms driving the increased postnatal hospitalizations, and educate health care professionals about the postnatal needs of women with IDD.

MAMA'S Neighborhood–Maternity Assessment Management Access &amp; Service Synergy Through the Neighborhood for Health [16L

INTRODUCTION: MAMA's Neighborhood (MAMAs), funded by the Strong Start for Mothers and Newborns Initiative, aims to evaluate models of prenatal care to reduce preterm (PTB) and low birth weight (LBW). Using a medical home model in high prevalence areas of Los Angeles, MAMAs sought to better assess potential social determinants of PTB and LBW and organize care to address these risks via: 1. Collaborative care teams, 2. Risk stratified case management, 3. Population health management, and 4. Community engagement and care delivery with social-service agencies. METHODS: Data were collected December 2013–August 2016. MAMAs implemented a novel initial assessment with evidence-based screening tools for psychosocial risk factors, risk stratification, case management and population health tracking by collaborative care teams at 6 sites. Neighborhood services were linked for individualized care planning. RESULTS: A total of 3,214 women enrolled. This cohort exhibited disproportionately high rates of food insecurity (15%), depression (23%), anxiety (31%) and intimate partner violence (32%) when compared to the general obstetric population. All women received risk stratified case management, allocating services weekly to 4%, monthly to 23%, and trimesterly to 74% of the cohort. Neighborhood service referrals averaged 3.7 per participant for psychosocial needs. CONCLUSION: MAMAs Neighborhood successfully implemented evidence-based screening tools for psychosocial risk factors into prenatal care, risk stratify and manage population health. MAMAs also developed individualized care plans for pregnant women including services delivered by community-based agencies to meet social needs. This model, involving both health system and community partners, leverages a Neighborhood approach to optimize maternal-child health outcomes.

Noninvasive prenatal testing in the general obstetric population: clinical performance and counseling considerations in over 85000 cases

The article contains the results of the research, which set two main goals. The first is the determination of the actual indicators of the effectiveness of noninvasive prenatal studies and the development of counseling tools about the predictability of a positive outcome, taking into account certain clinical indicators and the a priori age risk of the mother. The second is the assessment of changes in the clinical and demographic population after the introduction of testing.Objective: The primary goal of this study was to provide clinically relevant information for appropriate patient counseling.Method: Demographics and test metrics were reviewed for 86 658 clinical cases. Outcome information was requested for samples reported as aneuploidy detected or suspected for chromosomes 21, 18, or 13; voluntary outcome reporting was encouraged for all discordant outcomes.Results: Of 86 658 cases, 85 298 (98.4%) met inclusion criteria for result reporting. Of the 1360 (1.6%) cancellations, only 101 (0.1%) were for technical reasons. Average time to result was 3.3 business days. Aneuploidy was detected or suspected in 2142 (2.5%) samples. For aneuploidy detected cases with known clinical outcomes, the overall positive predictive value was 83.5% (608/728); observed positive predictive values for trisomies 21, 18, and 13 ranged from 50.0 to 92.8%. As individual positive predictive values are determined by a patient’s prior risk, we developed a chart for counseling patients on positive predictive value based on maternal age.Conclusion: This large-scale report reinforces that noninvasive prenatal testing is a highly accurate screen for fetal aneuploidy in the general obstetric population. Test improvements have facilitated a reduction in failure rates, time to result, and borderline results/unclassifiable results. We have developed a positive predictive value counseling tool to ensure appropriate patient education, counseling, and clinical utilization.Funding sources: This study was funded by Illumina.Conflicts of interest: Authors of article are employees of and hold equity in Illumina.