Severe Maternal and Neonatal Morbidity Among Gestational Carriers : A Cohort Study.

Velez MP ，Ivanova M ，Shellenberger J ，Pudwell J ，Ray JG ... -  《-》

Preterm birth in assisted reproduction: the mediating role of hypertensive disorders in pregnancy.

To what extent can hypertensive disorders in pregnancy (HDP) explain the higher risk of preterm birth following frozen embryo transfer (frozen-ET) and fresh embryo transfer (fresh-ET) in ART compared with naturally conceived pregnancies? HDP did not contribute to the higher risk of preterm birth in pregnancies after fresh-ET but mediated 20.7% of the association between frozen-ET and preterm birth. Risk of preterm birth is higher after ART compared to natural conception. However, there is also a higher risk of HDP in pregnancies after ART compared to natural conception, in particular after frozen-ET. HDP increases the risk of both spontaneous and medically indicated preterm birth. It is not known to what extent the higher risk of preterm birth in ART-conceived pregnancies is mediated through HDP. This registry-based cohort study included singleton pregnancies from the Committee of Nordic ART and Safety (CoNARTaS) cohort from Denmark (1994-2014), Norway (1988-2015), and Sweden (1988-2015). The analysis included 78 300 singletons born after fresh-ET, 18 037 after frozen-ET, and 4 426 682 after natural conception. The exposure was ART conception with either frozen-ET or fresh-ET versus natural conception. The main mediator of interest was any of the following HDP: gestational hypertension, preeclampsia, eclampsia, or chronic hypertension with superimposed preeclampsia. The main outcome was any preterm birth, defined as delivery <37 weeks of gestation. Secondary outcomes were spontaneous and medically indicated preterm birth, and different severities of preterm birth based on the gestational age threshold. We linked data from the national Medical Birth Registries, ART registries/databases, and the National Patient Registries in each country using the unique national identity number of the mother. Criteria for inclusion were singleton pregnancies with birth order 1-4 in women aged ≥20 years at delivery. We used logistic regression to estimate odds ratios (ORs) with 95% CIs of preterm birth and decomposed the total effect into direct and mediated (indirect) effects to estimate the proportion mediated by HDP. Main models included adjustment for the year of delivery, maternal age, parity, and country. Pregnancies following frozen-ET had a higher risk of any preterm birth compared to natural conception (occurrence 6.6% vs 5.0%, total effect OR 1.29, 95% CI 1.21-1.37) and 20.7% of the association was mediated by HDP (mediated effect OR 1.05, 95% CI 1.04-1.05). The mediation occurred primarily in medically indicated preterm births. Pregnancies following fresh-ET also had a higher risk of any preterm birth compared to naturally conceived pregnancies (occurrence 8.1% vs 5.0%, total effect OR 1.49, 95% CI: 1.45-1.53), but none of this could be mediated by HDP (mediated effect OR 1.00, 95%CI 1.00-1.00, proportion mediated 0.5%). Sensitivity analyses with extra confounder adjustment for body mass index and smoking, and restriction to primiparous women, were consistent with our main findings. Furthermore, the results were not driven by differences in ART procedures (intracytoplasmic sperm injection, culture duration, or the number of embryos transferred). Although we could adjust for some important confounders, we cannot exclude residual confounding, particularly from factors associated with infertility. This population-based mediation analysis suggests that some of the higher risk of preterm birth after ART treatment may be explained by the higher risk of HDP after frozen-ET. If causality is established, investigations into preventive strategies such as prophylactic aspirin in pregnancies after frozen-ET may be warranted. Funding was provided by NordForsk (project number: 71450), the Nordic Federation of Obstetrics and Gynaecology (project numbers NF13041, NF15058, NF16026, and NF17043), the Norwegian University of Science and Technology (project number 81850092), an ESHRE Grant for research in reproductive medicine (grant number 2022-2), and the Research Council of Norway's Centres of Excellence funding scheme (project number 262700). D.A.L.'s and A.E.'s contribution to this work was supported by the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreements No 101021566) and the UK Medical Research Council (MC_UU_00032/05). D.A.L. has received support from Roche Diagnostics and Medtronic Ltd for research unrelated to that presented here. Pinborg declares grants from Gedeon Richter, Ferring, Cryos, and Merck, consulting fees from IBSA, Ferring, Gedeon Richter, Cryos, and Merck, payments from Gedeon Richter, Ferring, Merck, and Organon,travel support from Gedeon Richter. All other authors declare no conflicts of interest related to this work. ISRCTN 35879.

Petersen SH ，Åsvold BO ，Lawlor DA ，Pinborg A ，Spangmose AL ，Romundstad LB ，Bergh C ，Wennerholm UB ，Gissler M ，Tiitinen A ，Elhakeem A ，Opdahl S ... -  《-》

Diagnostic properties of differing BP thresholds for adverse pregnancy outcomes in standard-risk nulliparous women: A secondary analysis of SCOPE cohort data.

In 2017, the American College of Cardiology and American Heart Association (ACC/AHA) lowered blood pressure (BP) thresholds to define hypertension in adults outside pregnancy. If used in pregnancy, these lower thresholds may identify women at increased risk of adverse outcomes, which would be particularly useful to risk-stratify nulliparous women. In this secondary analysis of the SCOPE cohort, we asked whether, among standard-risk nulliparous women, the ACC/AHA BP categories could identify women at increased risk for adverse outcomes. Included were pregnancies in the international SCOPE cohort with birth at ≥20 weeks' gestation, 2004 to 2008. Women were mostly of white ethnicity, in their 20s, and of normal-to-overweight body mass index (BMI). Excluded were pregnancies ending in fetal loss at <20 weeks' gestation, and those terminated at any point in pregnancy. Women were categorized by highest BP during pregnancy, using ACC/AHA criteria: normal (BP <120/80 mmHg), "Elevated BP" (BP 120 to 129 mmHg/<80 mmHg), "Stage-1 hypertension" (systolic BP [sBP] 130 to 139 mmHg or diastolic BP [dBP] 80 to 89 mmHg), and "Stage-2 hypertension" that was non-severe (sBP 140 to 159 mmHg or dBP 90 to 109 mmHg) or severe (sBP ≥160 mmHg or dBP ≥110 mmHg). Primary outcomes were preterm birth (PTB), low birthweight, postpartum hemorrhage, and neonatal care admission. Adjusted relative risks (aRRs) and diagnostic test properties were calculated for each outcome, according to: each BP category (versus "normal"), and using the lower limit of each BP category as a cut-off. RRs were adjusted for maternal age, BMI, smoking, ethnicity, and alcohol use. Of 5,628 women in SCOPE, 5,597 were included in this analysis. When compared with normotension, severe "Stage 2 hypertension" was associated with PTB (24.0% versus 5.3%; aRR 4.88, 95% confidence interval, CI [3.46 to 6.88]), birthweight <10th centile (24.4% versus 8.8%; aRR 2.70 [2.00 to 3.65]), and neonatal unit admission (32.9% versus 8.9%; aRR 3.40 [2.59 to 4.46]). When compared with normotension, non-severe "Stage 2 hypertension" was associated with birthweight <10th centile (16.1% versus 8.8%; aRR 1.82 [1.45 to 2.29]) and neonatal unit admission (15.4% versus 8.9%; aRR 1.65 [1.31 to 2.07]), but no association with adverse outcomes was seen with BP categories below "Stage 2 hypertension." When each BP category was assessed as a threshold for diagnosis of abnormal BP (compared with BP values below), only severe "Stage 2 hypertension" had a useful (good) likelihood ratio (LR) of 5.09 (95% CI [3.84 to 6.75]) for PTB. No BP threshold could rule-out adverse outcomes (i.e., had a negative LR <0.2). Limitations of our analysis include lack of ethnic diversity and use of values from clinical notes for BP within 2 weeks before birth. This study was limited by: its retrospective nature, not all women having BP recorded at all visits, and the lack of detail about some outcomes. In this study, we observed that 2017 ACC/AHA BP categories demonstrated a similar pattern of association and diagnostic test properties in nulliparous women, as seen in the general obstetric population. BP thresholds below the currently used "Stage 2 hypertension" were not associated with PTB, low birthweight, postpartum hemorrhage, or neonatal unit admission. This study does not support implementation of lower BP values as abnormal in nulliparous pregnant women.

Slade L ，Blackman M ，Mistry HD ，Bone JN ，Wilson M ，Syeda N ，Poston L ，von Dadelszen P ，Magee LA ，SCOPE Consortium ... -  《-》

Postpartum hospital use among survivors of intimate partner violence.

More than 1 in 3 individuals who identify as female, experience either intimate partner violence (IPV) or sexual assault during their lifetime, and sexual violence committed by an intimate partner is at its highest during their reproductive years.1 As many as 20% of pregnant individuals may experience IPV, and IPV during pregnancy has been associated with an increased risk for adverse maternal and neonatal outcomes, making pregnant individuals an especially vulnerable population.1 In fact, >50% of pregnancy-associated suicides and >45% of pregnancy-associated homicides are associated with IPV and these often occur during the postpartum period.2 Although >50% of maternal deaths occur postpartum,3 little research has examined whether IPV is associated with markers of postpartum maternal morbidity, including hospital readmission and emergency department (ED) visits.4 In addition, few studies have examined the feasibility of ascertaining IPV at the delivery hospitalization using billing codes. Although the International Classification of Diseases, Tenth Revision (ICD-10) codes include factors related to social determinants of health, ICD-10 codes are largely underutilized for the purpose of understanding risk of disease and adverse outcomes.5 The primary objective of this study was to investigate the association of IPV screening at delivery with the incidence of postpartum hospital use. Another objective was to examine the possibility of using ICD-10 codes at the delivery hospitalization to identify IPV in pregnant individuals. This was a retrospective cohort of birth data linked with inpatient and outpatient hospital claims data, including deliveries of individuals residing in the New York City metropolitan area between 2016 and 2018. Thirty-day hospital use was ascertained by either a readmission or an ED visit within 30 days of discharge. We identified the incidence of IPV from the delivery hospital discharge records using 36 IPV-related ICD-10 codes that we identified in the literature, including those defined for adult psychological and sexual abuse. We estimated the associations between IPV identified during the delivery hospitalization and postpartum hospital use using a multivariable logistic regression and separately adjusting for demographic and structural determinants of health, psychosocial factors, comorbidities, and obstetrical complications. All analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC). This study was approved by our institutional review board. IPV was indicated on the discharge records of 348 individuals (0.11%). As shown in the Table, the overall incidence of ED visits among individuals with an IPV-related diagnosis was 12.9%. The incidence of a postpartum ED visit was significantly higher among individuals with an IPV diagnosis than among those without (odds ratio [OR], 2.8; 95% confidence interval [CI], 2.1-3.9), and this was true after sequentially adjusting for demographic and structural determinants of health (OR, 2.0; 95% CI, 1.4-2.7), comorbidities and pregnancy complications (OR, 1.9; 95% CI, 1.4-2.6), psychosocial factors (OR, 1.5; 95% CI, 1.1-2.0), and obstetrical complications (OR, 1.5; 95% CI, 1.1-2.0). The incidence of either a postpartum ED visit or readmission was also higher among those patients with an IPV-related diagnosis (OR, 2.7; 95% CI, 2.0-3.6). However, there was no significant difference in postpartum readmissions alone among patients with or without an IPV-related diagnosis. This study established that postpartum ED visits are significantly higher among individuals with an IPV-related diagnosis during the delivery hospitalization in a large citywide database, even after adjusting for established risk factors for postpartum ED use. Because ED visits have been identified as a possible marker of maternal morbidity and mortality,4 this finding may suggest that individuals affected by IPV could benefit from screening throughout pregnancy, including during the delivery hospitalization, to prevent adverse postpartum outcomes. However, as established in this study, IPV identified solely by ICD-10 codes during the delivery hospitalization is rare and likely underreported. It is possible that underdetection of IPV is because of insufficient clinician screening, a lack of documentation in the medical records using ICD-10 codes, and the medical status of the pregnant individual at the time of delivery. This finding demonstrates a need to screen and record findings thoroughly during the pregnancy period, including at delivery hospitalization, for any IPV-related diagnoses. A limitation of our data is that we were not able to ascertain hospital use outside of New York City and did not include other time points during an individual's pregnancy. Future research should identify at which time points IPV screening occurs during care of a pregnant individual and whether this may affect postpartum ED visit rates. As a clinical outcome, maternal mortality is preventable and screening for risk factors such as IPV throughout the perinatal period, including at delivery admission and during the postpartum period, is imperative for comprehensive obstetrics care.

Rao MG ，Stone J ，Glazer KB ，Howell EA ，Janevic T ... -  《-》

Determining optimal timing of birth for women with chronic or gestational hypertension at term: The WILL (When to Induce Labour to Limit risk in pregnancy hypertension) randomised trial.

Chronic or gestational hypertension complicates approximately 7% of pregnancies, half of which reach 37 weeks' gestation. Early term birth (at 37 to 38 weeks) may reduce maternal complications, cesareans, stillbirths, and costs but may increase neonatal morbidity. In the WILL Trial (When to Induce Labour to Limit risk in pregnancy hypertension), we aimed to establish optimal timing of birth for women with chronic or gestational hypertension who reach term and remain well. This 50-centre, open-label, randomised trial in the United Kingdom included an economic analysis. WILL randomised women with chronic or gestational hypertension at 36 to 37 weeks and a singleton fetus, and who provided documented informed consent to "Planned early term birth at 38+0-3 weeks" (intervention) or "usual care at term" (control). The coprimary outcomes were "poor maternal outcome" (composite of severe hypertension, maternal death, or maternal morbidity; superiority hypothesis) and "neonatal care unit admission for ≥4 hours" (noninferiority hypothesis). The key secondary was cesarean. Follow-up was to 6 weeks postpartum. The planned sample size was 540/group. Analysis was by intention-to-treat. A total of 403 participants (37.3% of target) were randomised to the intervention (n = 201) or control group (n = 202), from 3 June 2019 to 19 December 2022, when the funder stopped the trial for delayed recruitment. In the intervention (versus control) group, losses to follow-up were 18/201 (9%) versus 15/202 (7%). In each group, maternal age was about 30 years, about one-fifth of women were from ethnic minorities, over half had obesity, approximately half had chronic hypertension, and most were on antihypertensives with normal blood pressure. In the intervention (versus control) group, birth was a median of 0.9 weeks earlier (38.4 [38.3 to 38.6] versus 39.3 [38.7 to 39.9] weeks). There was no evidence of a difference in "poor maternal outcome" (27/201 [13%] versus 24/202 [12%], respectively; adjusted risk ratio [aRR] 1.16, 95% confidence interval [CI] 0.72 to 1.87). For "neonatal care unit admission for ≥4 hours," the intervention was considered noninferior to the control as the adjusted risk difference (aRD) 95% CI upper bound did not cross the 8% prespecified noninferiority margin (14/201 [7%] versus 14/202 [7%], respectively; aRD 0.003, 95% CI -0.05 to +0.06), although event rates were lower-than-estimated. The intervention (versus control) was associated with no difference in cesarean (58/201 [29%] versus 72/202 [36%], respectively; aRR 0.81, 95% CI 0.61 to 1.08. There were no serious adverse events. Limitations include our smaller-than-planned sample size, and lower-than-anticipated event rates, so the findings may not be generalisable to where hypertension is not treated with antihypertensive therapy. In this study, we observed that most women with chronic or gestational hypertension required labour induction, and planned birth at 38+0-3 weeks (versus usual care) resulted in birth an average of 6 days earlier, and no differences in poor maternal outcome or neonatal morbidity. Our findings provide reassurance about planned birth at 38+0-3 weeks as a clinical option for these women. isrctn.com ISRCTN77258279.

Magee LA ，Kirkham K ，Tohill S ，Gkini E ，Moakes CA ，Dorling J ，Green M ，Hutcheon JA ，Javed M ，Kigozi J ，Mol BWM ，Singer J ，Hardy P ，Stubbs C ，Thornton JG ，von Dadelszen P ，WILL Trial Study Group ... -  《-》