Pre-eclampsia in a first pregnancy and subsequent pregnancy outcomes: a nationwide cohort study.

BACKGROUND: For women whose first pregnancy was complicated by pre-eclampsia (PE), particularly if severe and requiring early birth, the risk of recurrence and maternal and neonatal outcomes at subsequent birth are important considerations. METHODS: In this observational cohort study, all primiparous women who gave birth in Denmark between 1997 and 2016 were identified using nationwide registries. Women were stratified by whether they developed PE and followed from date of birth until subsequent birth, emigration, death or end of study (December 2016). The cumulative incidences of subsequent birth among women with versus without PE were assessed using the Aalen-Johansen estimator. Subsequent outcomes including PE recurrence and maternal and neonatal morbidity and mortality were also examined. Factors associated with subsequent birth and recurrent PE were examined using multivariable Cox regression models. RESULTS: Among 510 615 primiparous women with singleton pregnancies, 21 683 (4.2%) developed PE, with 1819 (0.4%) being early-onset PE (birth <34 weeks). Women with PE had a lower subsequent birth rate (57.4%) compared with women without PE (61.2%), and it was considerably lower among women with early-onset PE (49.4%). Among women with PE who had a subsequent birth, the overall recurrence rate of PE was 15.8% and higher among those with early-onset PE (31.5%). The gestational age increased with a median of 3 days (IQR -5 to 14) overall and 50 days (IQR 35-67) among those with early-onset PE. Moreover, neonatal and maternal morbidity and mortality were substantially improved in a subsequent pregnancy. CONCLUSIONS: Primiparous women with PE have a significantly lower rate of a subsequent birth than women without PE, yet the absolute difference was modest. Although the overall risk of recurrent PE is 1 in 6, maternal and neonatal morbidity and mortality at subsequent birth are substantially improved.

Vernix Caseosa Peritonitis Causing Acute Abdomen After Cesarean Section: A Case Series.

BACKGROUND Vernix caseosa peritonitis (VCP) is a rare complication that typically presents following an otherwise uneventful cesarean section. Leakage of vernix caseosa into the peritoneum is thought to elicit a granulomatous foreign body reaction. Symptoms can be similar to other acute abdominal conditions, and diagnosis is confirmed by intraoperative findings and histological examination. Peritoneal lavage with supportive measures is the mainstay of treatment and recovery. CASE REPORT Case 1 was a 30-year-old woman who developed right iliac fossa pain, fever, tachycardia, and tachypnea less than a week after her lower segment cesarean section (LSCS). She underwent a laparoscopy for a peritonitic abdomen and concern for intra-abdominal sepsis. A peritoneal biopsy demonstrated histological changes consistent with VCP. Case 2 was a 39-year-old woman who underwent a LSCS. After discharge, she re-presented with generalized abdominal pain. With computed tomography (CT) scan findings suggestive of appendicitis, an appendectomy was performed, and vernix caseosa was detected in all quadrants. Case 3 was a 33-year-old woman who presented with fever, vomiting, diarrhea, and iliac fossa pain 9 days following an LSCS. She was given analgesia and antibiotics for a pelvic fluid collection noted on CT scan. She re-presented with tense swelling and pain above her cesarean section incision. Laparoscopy revealed adhesions over the lower abdomen and pelvis and white plaques suggestive of vernix caseosa along the peritoneal side walls. CONCLUSIONS The rising incidence of cesarean births worldwide creates the potential for increased numbers of VCP cases. Greater recognition of VCP is warranted to prevent unnecessary procedures.

Dysregulation of Oxygen Sensing/Response Pathways in Pregnancies Complicated by Idiopathic Intrauterine Growth Restriction and Early-Onset Preeclampsia.

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are the leading causes of maternal and fetal morbidity/mortality. The central deficit in both conditions is impaired placentation due to poor trophoblast invasion, resulting in a hypoxic milieu in which oxidative stress contributes to the pathology. We examine the factors driving the hypoxic response in severely preterm PE (n = 19) and IUGR (n = 16) placentae compared to the spontaneous preterm (SPT) controls (n = 13) using immunoblotting, RT-PCR, immunohistochemistry, proximity ligation assays, and Co-IP. Both hypoxia-inducible factor (HIF)-1α and HIF-2α are increased at the protein level and functional in pathological placentae, as target genes prolyl hydroxylase domain (PHD)2, PHD3, and soluble fms-like tyrosine kinase-1 (sFlt-1) are increased. Accumulation of HIF-α-subunits occurs in the presence of accessory molecules required for their degradation (PHD1, PHD2, and PHD3 and the E3 ligase von Hippel-Lindau (VHL)), which were equally expressed or elevated in the placental lysates of PE and IUGR. However, complex formation between VHL and HIF-α-subunits is defective. This is associated with enhanced VHL/DJ1 complex formation in both PE and IUGR. In conclusion, we establish a significant mechanism driving the maladaptive responses to hypoxia in the placentae from severe PE and IUGR, which is central to the pathogenesis of both diseases.

Maternal and neonatal outcomes of women with gestational diabetes and without specific medical conditions: an Australian population-based study comparing induction of labor with expectant management.

BACKGROUND/AIMS: To evaluate maternal birth and neonatal outcomes among women with gestational diabetes mellitus (GDM), but without specific medical conditions and eligible for vaginal birth who underwent induction of labour (IOL) at term compared with those who were expectantly managed. MATERIALS AND METHODS: Population-based cohort study of women with GDM, but without medical conditions, who had a singleton, cephalic birth at 38-41 completed weeks gestation, in New South Wales, Australia between January 2010 and December 2016. Women who underwent IOL at 38, 39, 40 weeks gestation (38-, 39-, 40-induction groups) were compared with those who were managed expectantly and gave birth at and/or beyond the respective gestational age group (38-, 39-, 40-expectant groups). Multivariable logistic regression analysis was used to assess the association between IOL and adverse maternal birth and neonatal outcomes taking into account potential confounding by maternal age, country of birth, smoking, residential location, residential area of socioeconomic disadvantage and birth year. RESULTS: Of 676 762 women who gave birth during the study period, 66 606 (10%) had GDM; of these, 34799 met the inclusion criteria. Compared with expectant management, those in 38- (adjusted odds ratio (aOR) 1.11; 95% CI, 1.04-1.18), 39- (aOR 1.21; 95% CI, 1.14-1.28) and 40- (aOR 1.50; 95% CI, 1.40-1.60) induction groups had increased risk of caesarean section. Women in the 38-induction group also had an increased risk of composite neonatal morbidity (aOR 1.10; 95% CI, 1.01-1.21), which was not observed at 39- and 40-induction groups. We found no difference between groups in perinatal death or neonatal intensive care unit admission for births at any gestational age. CONCLUSION: In women with GDM but without specific medical conditions and eligible for vaginal birth, IOL at 38, 39, 40 weeks gestation is associated with an increased risk of caesarean section.

Stillbirth in Australia 2: Working together to reduce stillbirth in Australia: The Safer Baby Bundle initiative.

The rate of late gestation stillbirth in Australia is unacceptably high. Up to one third of stillbirths are preventable, particularly beyond 28 weeks' gestation. The aim of this second paper in the Stillbirth in Australia series is to highlight one key national initiative, the Safer Baby Bundle (SBB), which has been led by the Centre of Research Excellence in Stillbirth in partnership with state health departments. Addressing commonly identified evidence practice gaps, the SBB contains five elements that, when implemented together, should result in better outcomes than if performed individually. This paper describes the development of the SBB, what the initiative aims to achieve, and progress to date. By collaborating with Departments of Health and other partners to amplify uptake of the SBB, we anticipate a reduction of at least 20% in Australia's stillbirth rate after 28 weeks' gestation is achievable.

Venous thromboembolism prophylaxis during and following caesarean section: a survey of clinical practice.

BACKGROUND: Caesarean section (CS) is a significant risk factor for venous thromboembolism; however, the optimal method of thromboprophylaxis around the time of CS is unknown. AIMS: To examine current thromboprophylaxis practice during and following CS in Australia and New Zealand, and the willingness of obstetricians to participate in a randomised controlled trial (RCT) comparing different methods of thromboprophylaxis after CS. MATERIALS AND METHODS: An online survey was sent to fellows and trainees of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists. RESULTS: There were 488 responses from currently practising obstetricians (response rate 23.4%). During CS, 48% and 80% of obstetricians recommended intermittent pneumatic compression (IPC) and elastic stockings (ES), respectively. Following CS, 96-97% of obstetricians recommended early ambulation, 87-90% recommended ES, 23-36% recommended IPC, and 42-65% recommended low molecular weight heparin (LMWH) depending on clinical factors. Increased BMI (OR 3.42; 95% CI 2.87-4.06), emergency CS (OR 1.88; 95% CI 1.67-2.16) and older maternal age (OR 1.37; 95% CI 1.26-1.49) were associated with more frequent LMWH use. Of obstetricians who prescribed LMWH, 70% adjusted the dose depending on maternal weight. LMWH therapy was most commonly recommended until discharge from hospital (31%), <5 days (24%) and 5-7 days (15%). Most obstetricians (58-79%) were willing to enrol women in a RCT, but less likely if the woman had an increased BMI or emergency CS. CONCLUSIONS: There is considerable variation in clinical practice regarding thromboprophylaxis during and following CS. Obstetricians support a RCT to assess different methods of thromboprophylaxis following CS.

Trends and outcomes of postpartum haemorrhage, 2003-2011.

BACKGROUND: While rates of postpartum haemorrhage (PPH) have continued to rise, it is not clear if the association with other morbidity and transfusion has changed over time. This study explores the recent trend in postpartum haemorrhage and whether postpartum haemorrhage is associated with increased transfusions or adverse outcomes over time. METHODS: Linked birth and hospital data were used to examine ICD-10 AM coded PPH and outcomes in maternal birth admission records, 2003--2011 in hospitals in New South Wales (NSW), Australia (N = 818,965 pregnancies). Trends were calculated on the whole population, and among subgroups, and tested using the Cochran Armitage test for trend. Logistic regression models were developed separately for vaginal and caesarean births, and for a maternal morbidity composite indicator (excluding transfusion) and red cell transfusion. Adjusted odds ratios (aOR) for each year relative to 2003 and 95% confidence intervals (CI) are presented with adjustment for maternal (eg. age, country of birth) and pregnancy factors (eg. parity, interventions, pregnancy complications). RESULTS: Overall, there was a significant increase in the PPH rate, from 6.1% in 2003 to 8.3% in 2011 (p < 0.0001). Crude rates of postpartum haemorrhage with transfusion increased from 0.75% (n = 636) to 1.21% (n = 1145) (p < 0.0001) while crude rates of postpartum haemorrhage with maternal morbidity increased from 0.18% (n = 149) to 0.23% (n = 221) (p = 0.02). Having accounted for maternal and pregnancy factors, there were significant overall decreases in the odds of morbidity among women with a PPH delivering vaginally (in 2006, 2007 and 2010, aORs were 0.70 (95 % CI 0.52, 0.96) 0.69 (0.51, 0.94) and 0.64 (0.47, 0.87) relative to 2003; p < 0.05), and no significant decrease among women delivered by caesarean section (aOR 0.87 (0.58, 1.29) in 2011; p = 0.37). Among women with a PPH delivering vaginally, there was a trend towards a non-linear increase in the adjusted odds of transfusion by birth year. Compared to women who had vaginal births with PPH in 2003, the adjusted odds for transfusion was between 1.1 and 1.2 fold higher for those with a PPH delivering vaginally in 2007, 2009, 2010 and 2011. However there was no significant trend amongst caesarean births (aOR 0.84 (0.66, 1.06) in 2011; p = 0.29). CONCLUSIONS: PPH has become more frequent, however this has not been associated with a clear pattern of increased severe maternal morbidity. This suggests that the increase in PPH may represent fewer severe haemorrhages, better management of severe haemorrhage or better recording of PPH. The increase in transfusions following vaginal births with PPH warrants further investigation.