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Objectives: To estimate the association between chronic hypertension and perinatal mortality and to evaluate the extent to which risks are impacted by preterm delivery. Design: Cross‐sectional analysis. Setting: United States, 2015–18. Population: Singleton births (20–44 weeks of gestation). Exposure: Chronic hypertension, defined as elevated blood pressure diagnosed before pregnancy or recognised before 20 weeks of gestation. Main outcomes and measures: We derived the risk of perinatal mortality in relation to chronic hypertension from Poisson models, adjusted for confounders. The impacts of misclassification and unmeasured confounding were assessed. Causal mediation analysis was performed to quantify the impact of preterm delivery on the association. Results: Of the 15 090 678 singleton births, perinatal mortality rates were 22.5 and 8.2 per 1000 births in chronic hypertensive and normotensive pregnancies, respectively (adjusted risk ratio 2.05, 95% CI 2.00–2.10). Corrections for exposure misclassification and unmeasured confounding biases substantially increased the risk estimate. Although causal mediation analysis revealed that most of the association of chronic hypertension on perinatal mortality was mediated through preterm delivery, the perinatal mortality rates were highest at early term, term and late term gestations, suggesting that a planned early term delivery at 37–386/7 weeks may optimally balance risk in these pregnancies. Additionally, 87% (95% CI 84–90%) of perinatal deaths could be eliminated if preterm deliveries, as a result of chronic hypertension, were preventable. Conclusions: Chronic hypertension is associated with increased risk for perinatal mortality. Planned early term delivery and targeting modifiable risk factors for chronic hypertension may reduce perinatal mortality rates. Maternal chronic hypertension is associated with increased risk for perinatal mortality, largely driven by preterm birth. Maternal chronic hypertension is associated with increased risk for perinatal mortality, largely driven by preterm birth. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between maternal fructosamine levels at the time of delivery and stillbirth. Design: Secondary analysis of a case–control study. Setting: Multicentre study of five geographic catchment areas in the USA. Population: All singleton stillbirths with known diabetes status and fructosamine measurement, and representative live birth controls. Main outcome measures: Fructosamine levels in stillbirths and live births among groups were adjusted for potential confounding factors, including diabetes. Optimal thresholds of fructosamine to discriminate stillbirth and live birth. Results: A total of 529 women with a stillbirth and 1499 women with a live birth were included in the analysis. Mean fructosamine levels were significantly higher in women with a stillbirth than in women with a live birth after adjustment (177 ± 3.05 versus 165 ± 2.89 μmol/L, P < 0.001). The difference in fructosamine levels between stillbirths and live births was greater among women with diabetes (194 ± 8.54 versus 162 ± 3.21 μmol/L), compared with women without diabetes (171 ± 2.50 versus 162 ± 2.56 μmol/L). The area under the curve (AUC) for fructosamine level and stillbirth was 0.634 (0.605–0.663) overall, 0.713 (0.624–0.802) with diabetes and 0.625 (0.595–0.656) with no diabetes. Conclusions: Maternal fructosamine levels at the time of delivery were higher in women with stillbirth compared with women with live birth. Differences were substantial in women with diabetes, suggesting a potential benefit of glycaemic control in women with diabetes during pregnancy. The small differences noted in women without diabetes are not likely to justify routine screening in all cases of stillbirth. Maternal serum fructosamine levels are higher in women with stillbirth than in women with live birth, especially in women with diabetes. Maternal serum fructosamine levels are higher in women with stillbirth than in women live birth, especially in women with diabetes. [ABSTRACT FROM AUTHOR]

Objective: This study utilized the Dr. Foster Global Comparators database to identify pregnancy complications and associated risk factors that led to severe maternal morbidity during delivery hospitalisations in large university hospitals based in the USA, Australia, and England.Design: Retrospective cohort.Setting: Births in the USA, England and Australia from 2008 to 2013.Sample: Data from delivery hospitalisations between 2008 and 2013 were examined using the Dr. Foster Global Comparators database.Methods: We identified delivery hospitalisations with life-threatening diagnoses or use of life-saving procedures, using algorithms for severe maternal morbidity from the Center for Disease Control. Frequency of severe maternal morbidity was calculated for each country.Main Outcome Measures: Multivariable analysis was used to examine the association between morbidity and socio-demographic and clinical characteristics within each country. Chi-square tests assessed differences in covariates between countries.Results: From 2008 to 2013, there were 516 781 deliveries from a total of 18 hospitals: 24.5% from the USA, 57.0% from England and 18.4% from Australia. Overall severe maternal morbidity rate was 8.2 per 1000 deliveries: 15.6 in the USA, 5.0 in England, and 8.2 in Australia. The most common codes identifying severe morbidity included transfusion, disseminated intravascular coagulation, acute renal failure, cardiac events/procedures, ventilation, hysterectomy, and eclampsia. Advanced maternal age, hypertension, diabetes, and substance abuse were associated with severe maternal morbidity in all three countries.Conclusion: Rates of severe maternal morbidity differed by country. Identification of geographical, socio-demographic, and clinical differences can help target modifications of practice and potentially reduce severe maternal morbidity.Tweetable Abstract: Rates of severe maternal morbidity vary, but risk factors associated with adverse outcomes are similar in developed countries. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the incidence and risk of complications associated with a fetal scalp electrode and to determine whether its application in the setting of operative vaginal delivery was associated with increased neonatal morbidity.Design: Retrospective cohort study.Setting: Twelve clinical centers with 19 hospitals across nine American Congress of Obstetricians and Gynecologists US districts.Population: Women in the USA.Methods: We evaluated 171 698 women with singleton deliveries ≥ 23 weeks of gestation in a secondary analysis of the Consortium on Safe Labor study between 2002 and 2008, after excluding conditions that precluded fetal scalp electrode application such as prelabour caesarean delivery. Secondary analysis limited to operative vaginal deliveries ≥ 34 weeks of gestation was also performed.Main Outcome Measures: Incidences and adjusted odds ratios with 95% confidence intervals of neonatal complications were calculated, controlling for maternal characteristics, delivery mode and pregnancy complications.Results: Fetal scalp electrode was used in 37 492 (22%) of deliveries. In non-operative vaginal delivery, fetal scalp electrode was associated with increased risk of injury to scalp due to birth trauma (1.2% versus 0.9%; adjusted odds ratios 1.62; 95% confidence intervals 1.41-1.86) and cephalohaematoma (1.0% versus 0.9%; adjusted odds ratios 1.57; 95% confidence intervals 1.36-1.83). Neonatal complications were not significantly different comparing fetal scalp electrode with vacuum-assisted vaginal delivery and vacuum-assisted vaginal delivery alone or comparing fetal scalp electrode with forceps-assisted vaginal delivery and forceps-assisted vaginal delivery alone.Conclusions: We found increased neonatal morbidity with fetal scalp electrode though the absolute risk was very low. It is possible that these findings reflect an underlying indication for its use. Our findings support the use of fetal scalp electrodes when clinically indicated.Tweetable Abstract: Neonatal risks associated with fetal scalp electrode use were low (injury to scalp 1.2% and cephalohaematoma 1.0%). [ABSTRACT FROM AUTHOR]

Objective To determine whether β2-adrenoceptor ( β2 AR) genotype is associated with shortening of the cervix or with preterm birth ( PTB) risk among women with a short cervix in the second trimester. Design A case-control ancillary study to a multicentre randomised controlled trial. Setting Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Population Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. Methods Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. β2 AR genotype was determined at positions encoding for amino acid residues 16 and 27. Main outcome measures Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks. Results Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity ( OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity ( OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. Conclusions β2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with β2 AR genotype do not appear to involve a short cervix pathway. [ABSTRACT FROM AUTHOR]

The author reflects on the study on the relationship between previous caesarean delivery and the risk of unexplained antepartum stillbirth in the second pregnancy. The study involved a cohort of singleton births in Scotland and the national registry Scottish Stillbirth and Infant Death Survey. The results reportedly revealed that women with previous caesarean delivery are more at risk of unexplained stillbirth in the second pregnancy compared with those who had normal delivery.

Please cite this paper as: Herring A, Reddy U. Recurrence risk of stillbirth in the second pregnancy. BJOG 2010;117:1173–1174. [ABSTRACT FROM AUTHOR]

Objective: To examine the association of placental and fetal DNA copy number variants (CNVs) with fetal structural malformations (FSMs) in stillborn fetuses., Design: A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network (SCRN) study., Setting: Multicenter, 59 hospitals in five geographic regions in the USA., Population: 388 stillbirth cases of the SCRN study (2006-2008)., Methods: Fetal structural malformations were grouped by anatomic system and specific malformation type (e.g. central nervous system, thoracic, cardiac, gastrointestinal, skeletal, umbilical cord and craniofacial defects). Single-nucleotide polymorphism array detected CNVs of at least 500 kb. CNVs were classified into two groups: normal, defined as no CNVs >500 kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance., Main Outcome Measures: The proportions of abnormal CNVs and normal CNVs were compared between stillbirth cases with and without FSMs using the Wald Chi-square test., Results: The proportion of stillbirth cases with any FSMs was higher among those with abnormal CNVs than among those with normal CNVs (47.5 versus 19.1%; P-value <0.001). The most common organ system-specific FSMs associated with abnormal CNVs were cardiac defects, followed by hydrops, craniofacial defects and skeletal defects. A pathogenic deletion of 1q21.1 involving 46 genes (e.g. CHD1L) and a duplication of 21q22.13 involving four genes (SIM2, CLDN14, CHAF1B, HLCS) were associated with a skeletal and cardiac defect, respectively., Conclusion: Specific CNVs involving several genes were associated with FSMs in stillborn fetuses. The findings warrant further investigation and may inform counselling and care surrounding pregnancies affected by FSMs at risk for stillbirth., (© 2023 John Wiley & Sons Ltd.)

Objective: To examine the association of fetal/placental DNA copy number variants (CNVs) with pathologic placental lesions (PPLs) in pregnancies complicated by stillbirth., Design: A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network case-control study., Setting: Multicenter, 59 hospitals in five geographical regions in the USA., Population: 387 stillbirth cases (2006-2008)., Methods: Using standard definitions, PPLs were categorised by type including maternal vascular, fetal vascular, inflammatory and immune/idiopathic lesions. Single-nucleotide polymorphism array detected CNVs of at least 500 kb. CNVs were classified into two groups: normal, defined as no CNV >500 kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance., Main Outcome Measures: The proportions of abnormal CNVs and normal CNVs compared between stillbirth cases with and without PPLs using the Wald Chi-square test., Results: Of 387 stillborn fetuses, 327 (84.5%) had maternal vascular PPLs and 60 (15.6%) had abnormal CNVs. Maternal vascular PPLs were more common in stillborn fetuses with abnormal CNVs than in those with normal CNVs (81.7% versus 64.2%; P = 0.008). The proportions of fetal vascular, maternal/fetal inflammatory and immune/idiopathic PPLs were similar among stillborn fetuses with abnormal CNVs and those with normal CNVs. Pathogenic CNVs in stillborn fetuses with maternal vascular PPLs spanned several known genes., Conclusions: Abnormal placental/fetal CNVs were associated with maternal vascular PPLs in stillbirth cases. The findings may provide insight into the mechanisms of specific genetic abnormalities associated with placental dysfunction and stillbirth., (© 2022 John Wiley & Sons Ltd.)

Objective: To evaluate whether hypertensive disorders of pregnancy (HDP) among low-risk nulliparous women expectantly managed at or after 39 weeks of gestation are associated with adverse outcomes., Design: Secondary analysis of a randomised trial., Setting: Multicentre, USA., Population: Individuals in the expectantly managed group who delivered on or after 39 weeks., Methods: Multivariable analysis to estimate adjusted relative risks (aRR) for binomial outcomes, adjusted odds ratios (aOR) for multinomial outcomes and 95% CI., Main Outcome Measures: Composite adverse maternal outcome including placental abruption, pulmonary oedema, postpartum haemorrhage, postpartum infection, venous thromboembolism or intensive care unit admission. Secondary outcomes included a composite of perinatal death or severe neonatal complications, mode of delivery, small and large for gestational age and neonatal intermediate or intensive unit length of stay., Results: Of the 3044 women randomised to expectant management in the original trial, 2718 (89.3%) were eligible for this analysis, of whom 373 (13.7%) developed HDP. Compared with participants who remained normotensive, those who developed HDP were more likely to experience the maternal composite (12% versus 6%, aRR 1.84, 95% CI 1.33-2.54) and caesarean delivery (29% versus 23%, aOR 1.32, 95% CI 1.01-1.71). Differences between the two groups were not significantly different for the adverse perinatal composite (7% versus 5%, aRR 1.38, 95% CI 0.92-2.07) or for other secondary outcomes., Conclusion: Almost 14% of low-risk nulliparous individuals expectantly managed at 39 weeks developed HDP, and were more likely to experience adverse maternal outcomes compared with those who did not develop HDP., Tweetable Abstract: Almost 14% of low-risk nulliparous individuals expectantly managed at 39 weeks developed hypertensive disorders of pregnancy, and were more likely to experience adverse maternal outcomes compared with those who did not develop hypertensive disorders., (© 2021 John Wiley & Sons Ltd.)

Background Our objective was to assess new chronic hypertension 6 to 12 months postpartum for those with hypertensive disorder of pregnancy (HDP) compared with normotensive participants. Methods and Results We performed a prospective cohort study of participants with singleton gestations and no known preexisting medical conditions who were diagnosed with HDP compared with normotensive women with no pregnancy complications (non-HDP). Participants underwent cardiovascular risk assessment 6 to 12 months after delivery. Primary outcome was onset of new chronic hypertension at 6 to 12 months postpartum. We also examined lipid values, metabolic syndrome, prediabetes, diabetes, and 30-year cardiovascular disease (CVD) risk. Multivariable logistic regression was performed to assess the association between HDP and odds of a postpartum diagnosis of chronic hypertension while adjusting for parity, body mass index, insurance, and family history of CVD. There were 58 participants in the HDP group and 51 participants in the non-HDP group. Baseline characteristics between groups were not statistically different. Participants in the HDP group had 4-fold adjusted odds of developing a new diagnosis of chronic hypertension 6 to 12 months after delivery, compared with those in the non-HDP group (adjusted odds ratio, 4.60 [95% CI, 1.65-12.81]), when adjusting for body mass index, parity, family history of CVD, and insurance. Of the HDP group, 58.6% (n=34) developed new chronic hypertension. Participants in the HDP group had increased estimated 30-year CVD risk and were more likely to have metabolic syndrome, a higher fasting blood glucose, and higher low-density lipoprotein cholesterol. Conclusions Participants without known underlying medical conditions who develop HDP have 4-fold increased odds of new diagnosis of chronic hypertension by 6 to 12 months postpartum as well as increased 30-year CVD risk scores. Implementation of multidisciplinary care models focused on CVD screening, patient education, and lifestyle interventions during the first year postpartum may serve as an effective primary prevention strategy for the development of CVD.

Objective: To evaluate the association between maternal fructosamine levels at the time of delivery and stillbirth., Design: Secondary analysis of a case-control study., Setting: Multicentre study of five geographic catchment areas in the USA., Population: All singleton stillbirths with known diabetes status and fructosamine measurement, and representative live birth controls., Main Outcome Measures: Fructosamine levels in stillbirths and live births among groups were adjusted for potential confounding factors, including diabetes. Optimal thresholds of fructosamine to discriminate stillbirth and live birth., Results: A total of 529 women with a stillbirth and 1499 women with a live birth were included in the analysis. Mean fructosamine levels were significantly higher in women with a stillbirth than in women with a live birth after adjustment (177 ± 3.05 versus 165 ± 2.89 μmol/L, P < 0.001). The difference in fructosamine levels between stillbirths and live births was greater among women with diabetes (194 ± 8.54 versus 162 ± 3.21 μmol/L), compared with women without diabetes (171 ± 2.50 versus 162 ± 2.56 μmol/L). The area under the curve (AUC) for fructosamine level and stillbirth was 0.634 (0.605-0.663) overall, 0.713 (0.624-0.802) with diabetes and 0.625 (0.595-0.656) with no diabetes., Conclusions: Maternal fructosamine levels at the time of delivery were higher in women with stillbirth compared with women with live birth. Differences were substantial in women with diabetes, suggesting a potential benefit of glycaemic control in women with diabetes during pregnancy. The small differences noted in women without diabetes are not likely to justify routine screening in all cases of stillbirth., Tweetable Abstract: Maternal serum fructosamine levels are higher in women with stillbirth than in women with live birth, especially in women with diabetes., (© 2021 John Wiley & Sons Ltd.)

Objectives: To estimate the association between chronic hypertension and perinatal mortality and to evaluate the extent to which risks are impacted by preterm delivery., Design: Cross-sectional analysis., Setting: United States, 2015-18., Population: Singleton births (20-44 weeks of gestation)., Exposure: Chronic hypertension, defined as elevated blood pressure diagnosed before pregnancy or recognised before 20 weeks of gestation., Main Outcomes and Measures: We derived the risk of perinatal mortality in relation to chronic hypertension from Poisson models, adjusted for confounders. The impacts of misclassification and unmeasured confounding were assessed. Causal mediation analysis was performed to quantify the impact of preterm delivery on the association., Results: Of the 15 090 678 singleton births, perinatal mortality rates were 22.5 and 8.2 per 1000 births in chronic hypertensive and normotensive pregnancies, respectively (adjusted risk ratio 2.05, 95% CI 2.00-2.10). Corrections for exposure misclassification and unmeasured confounding biases substantially increased the risk estimate. Although causal mediation analysis revealed that most of the association of chronic hypertension on perinatal mortality was mediated through preterm delivery, the perinatal mortality rates were highest at early term, term and late term gestations, suggesting that a planned early term delivery at 37-38 6/7  weeks may optimally balance risk in these pregnancies. Additionally, 87% (95% CI 84-90%) of perinatal deaths could be eliminated if preterm deliveries, as a result of chronic hypertension, were preventable., Conclusions: Chronic hypertension is associated with increased risk for perinatal mortality. Planned early term delivery and targeting modifiable risk factors for chronic hypertension may reduce perinatal mortality rates., Tweetable Abstract: Maternal chronic hypertension is associated with increased risk for perinatal mortality, largely driven by preterm birth., (© 2021 John Wiley & Sons Ltd.)

Background Cardiovascular risk in young adulthood is an important determinant of lifetime cardiovascular disease risk. Women with adverse pregnancy outcomes (APOs) have increased cardiovascular risk, but the relationship of other factors is unknown. Methods and Results Among 4471 primiparous women, we related first-trimester atherogenic markers to risk of APO (hypertensive disorders of pregnancy, preterm birth, small for gestational age), gestational diabetes mellitus (GDM) and hypertension (130/80 mm Hg or antihypertensive use) 2 to 7 years after delivery. Women with an APO/GDM (n=1102) had more atherogenic characteristics (obesity [34.2 versus 19.5%], higher blood pressure [systolic blood pressure 112.2 versus 108.4, diastolic blood pressure 69.2 versus 66.6 mm Hg], glucose [5.0 versus 4.8 mmol/L], insulin [77.6 versus 60.1 pmol/L], triglycerides [1.4 versus 1.3 mmol/L], and high-sensitivity C-reactive protein [5.6 versus 4.0 nmol/L], and lower high-density lipoprotein cholesterol [1.8 versus 1.9 mmol/L]; P <0.05) than women without an APO/GDM. They were also more likely to develop hypertension after delivery (32.8% versus 18.1%, P <0.05). Accounting for confounders and factors routinely assessed antepartum, higher glucose (relative risk [RR] 1.03 [95% CI, 1.00-1.06] per 0.6 mmol/L), high-sensitivity C-reactive protein (RR, 1.06 [95% CI, 1.02-1.11] per 2-fold higher), and triglycerides (RR, 1.27 [95% CI, 1.14-1.41] per 2-fold higher) were associated with later hypertension. Higher physical activity was protective (RR, 0.93 [95% CI, 0.87-0.99] per 3 h/week). When evaluated as latent profiles, the nonobese group with higher lipids, high-sensitivity C-reactive protein, and insulin values (6.9% of the cohort) had increased risk of an APO/GDM and later hypertension. Among these factors, 7% to 15% of excess RR was related to APO/GDM. Conclusions Individual and combined first-trimester atherogenic characteristics are associated with APO/GDM occurrence and hypertension 2 to 7 years later. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02231398.

Background Identifying pregnancy-associated risk factors before the development of major cardiovascular disease events could provide opportunities for prevention. The objective of this study was to determine the association between outcomes in first pregnancies and subsequent cardiovascular health. Methods and Results The Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be Heart Health Study is a prospective observational cohort that followed 4484 women 2 to 7 years (mean 3.2 years) after their first pregnancy. Adverse pregnancy outcomes (defined as hypertensive disorders of pregnancy, small-for-gestational-age birth, preterm birth, and stillbirth) were identified prospectively in 1017 of the women (22.7%) during this pregnancy. The primary outcome was incident hypertension (HTN). Women without adverse pregnancy outcomes served as controls. Risk ratios (RR) and 95% CIs were adjusted for age, smoking, body mass index, insurance type, and race/ethnicity at enrollment during pregnancy. The overall incidence of HTN was 5.4% (95% CI 4.7% to 6.1%). Women with adverse pregnancy outcomes had higher adjusted risk of HTN at follow-up compared with controls (RR 2.4, 95% CI 1.8-3.1). The association held for individual adverse pregnancy outcomes: any hypertensive disorders of pregnancy (RR 2.7, 95% CI 2.0-3.6), preeclampsia (RR 2.8, 95% CI 2.0-4.0), and preterm birth (RR 2.7, 95% CI 1.9-3.8). Women who had an indicated preterm birth and hypertensive disorders of pregnancy had the highest risk of HTN (RR 4.3, 95% CI 2.7-6.7). Conclusions Several pregnancy complications in the first pregnancy are associated with development of HTN 2 to 7 years later. Preventive care for women should include a detailed pregnancy history to aid in counseling about HTN risk. Clinical Trial Registration URL: http://www.clinicaltrials.gov Unique identifier: NCT02231398.

Objective: This study utilized the Dr. Foster Global Comparators database to identify pregnancy complications and associated risk factors that led to severe maternal morbidity during delivery hospitalisations in large university hospitals based in the USA, Australia, and England., Design: Retrospective cohort., Setting: Births in the USA, England and Australia from 2008 to 2013., Sample: Data from delivery hospitalisations between 2008 and 2013 were examined using the Dr. Foster Global Comparators database., Methods: We identified delivery hospitalisations with life-threatening diagnoses or use of life-saving procedures, using algorithms for severe maternal morbidity from the Center for Disease Control. Frequency of severe maternal morbidity was calculated for each country., Main Outcome Measures: Multivariable analysis was used to examine the association between morbidity and socio-demographic and clinical characteristics within each country. Chi-square tests assessed differences in covariates between countries., Results: From 2008 to 2013, there were 516 781 deliveries from a total of 18 hospitals: 24.5% from the USA, 57.0% from England and 18.4% from Australia. Overall severe maternal morbidity rate was 8.2 per 1000 deliveries: 15.6 in the USA, 5.0 in England, and 8.2 in Australia. The most common codes identifying severe morbidity included transfusion, disseminated intravascular coagulation, acute renal failure, cardiac events/procedures, ventilation, hysterectomy, and eclampsia. Advanced maternal age, hypertension, diabetes, and substance abuse were associated with severe maternal morbidity in all three countries., Conclusion: Rates of severe maternal morbidity differed by country. Identification of geographical, socio-demographic, and clinical differences can help target modifications of practice and potentially reduce severe maternal morbidity., Tweetable Abstract: Rates of severe maternal morbidity vary, but risk factors associated with adverse outcomes are similar in developed countries., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Objective: To compare maternal genotypes between women with and without significant prolongation of pregnancy in the setting of 17-alpha hydroxyprogesterone caproate (17-P) administration for the prevention of recurrent preterm birth (PTB)., Design: Case-control., Setting: Three tertiary-care centres across the USA., Population: Women (n = 99) with ≥ 1 prior singleton spontaneous PTB, receiving 17-P., Methods: Women were classified as having successful prolongation of pregnancy during the 17-P treated pregnancy, in two ways: (1) Definition A: success/non-success based on difference in gestational age at delivery between 17-P-treated and untreated pregnancies (success: delivered ≥ 3 weeks later with 17-P) and (2) Definition B: success/non-success based on reaching term (success: delivered at term with 17-P)., Main Outcome Measures: To assess genetic variation, all women underwent whole exome sequencing. Between-group sequence variation was analysed with the Variant Annotation, Analysis, and Search Tool (VAAST). Genes scored by VAAST with P < 0.05 were then analysed with two online tools: (1) Protein ANalysis THrough Evolutionary Relationships (PANTHER) and (2) Database for Annotation, Visualization, and Integrated Discovery (DAVID)., Results: Using Definition A, there were 70 women with successful prolongation and 29 without; 1375 genes scored by VAAST had P < 0.05. Using Definition B, 47 women had successful prolongation and 52 did not; 1039 genes scored by VAAST had P < 0.05. PANTHER revealed key differences in gene ontology pathways. Many genes from definition A were classified as prematurity genes (P = 0.026), and those from definition B as pharmacogenetic genes (P = 0.0018); (P, non-significant after Bonferroni correction)., Conclusion: A novel analytic approach revealed several genetic differences among women delivering early vs later with 17-P., Tweetable Abstract: Several key genetic differences are present in women with recurrent preterm birth despite 17-P treatment., (© 2017 Royal College of Obstetricians and Gynaecologists.)

Objective: To determine whether β2 -adrenoceptor (β2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester., Design: A case-control ancillary study to a multicentre randomised controlled trial., Setting: Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development., Population: Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length., Methods: Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. β2 AR genotype was determined at positions encoding for amino acid residues 16 and 27., Main Outcome Measures: Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks., Results: Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited., Conclusions: β2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with β2 AR genotype do not appear to involve a short cervix pathway., (© 2015 Royal College of Obstetricians and Gynaecologists.)