The Indonesia pre-eclampsia study (INAPRES): Pregnancy outcomes in pregnancy with pre-eclampsia in Indonesia.

Pathogenesis of the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP): a review

BACKGROUNDIndices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), platelet distribution width (PDW), and red cell distribution width (RDW) are considered new markers of the systemic inflammatory response (SIR), and have been widely implemented for the diagnosis of patients with inflammatory diseases. These new indicators have also been widely investigated in preeclampsia (PE) but less analyzed in hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome.AIMTo compare SIR markers among HELLP patients, PE only patients, and healthy gravidae.METHODSThis retrospective case-control study enrolled 630 cases, including 210 patients with HELLP syndrome (HELLP group), 210 patients with only PE (PE group) and 210 healthy gravidae (control group). The three groups were matched by age, parity, status of assisted reproduction, and multiple pregnancies. Birthweight, gestational age at complete blood count collection, gestational age at delivery, mode of delivery, etc. were recorded. The main indices as NLR, PLR, MPV, PDW, and RDW among the groups were compared, as well as some secondary outcomes including neutrophil, platelets, and hemoglobin.RESULTSThe NLR (6.4 vs 4.3 vs 3.5), MPV (11.9 vs 11.2 vs 10.7), PDW (16.4 vs 13.3 vs 14.2), leukocyte (12.4 × 109/L vs 9.7 × 109/L vs 8.7 × 109/L) and neutrophil count (9.9 × 109/L vs 7.3 × 109/L vs 6.1 × 109/L) were highest in the HELLP group, lower in the PE group, and lowest in the control group. Both the overall comparisons between the three groups (all bP < 0.01) and pairwise comparisons between every two groups elicited statistically significant differences (all dP < 0.01, except control vs PE: cP < 0.05 in PDW). The average lymphocyte counts were 1.4 (1.1, 2.0) × 109/L in the HELLP group, 1.6 (1.3, 2.0) × 109/L in the PE group and 1.7 (1.4, 2.0) × 109/L in the control group. The overall comparison of lymphocyte count within the three groups had statistically significant differences (P = 0.000). The pairwise comparisons between every two groups demonstrated that the HELLP group had a lower lymphocyte count than both the PE (P = 0.019) and control groups (P = 0.000), but the difference between the PE and control groups was not statistically significant (P = 0.432). The overall comparisons on platelet counts and the PLR among these three groups also showed statistically significant differences (both P = 0.000), from low to high being those in the HELLP group (43.4 × 109/L, 64.0), control group (180.5 × 109/L, 103.6) and PE group (181.5 × 109/L, 112.8). Pairwise comparisons of neither index displayed statistically significant differences between the PE and control groups (both P > 0.05), while the differences in the two indices between the HELLP group and the two other groups were still statistically significant (all P = 0.000). RDW values were highest in the HELLP group (14.5% [13.6, 15.3]), lower in the control group (14.1% [13.5, 14.8]) and lowest in the PE group (13.9% [13.4, 14.9]). The difference between the PE and control group did not show statistical significance (P = 1.000), while RDW values in the HELLP group were higher than those in the other two groups (cP < 0.05 vs control, dP < 0.01 vs PE).CONCLUSIONSIR markers such as NLR, RDW, MPV, and PDW were increased and PLR was decreased in HELLP. These SIR markers may become new indicators in the evaluation of HELLP syndrome.

Pre-eclampsia (PE) is a pregnancy-specific syndrome that is the principal cause of maternal morbidity and mortality, accounting for almost 15% of pregnancy-associated deaths (American College of Obstetricians and Gynecologists 1996). Hippocrates first described the condition when he wrote in one of his Aphorisms that ‘convulsions take place from either repletion or depletion’ (Salas 1999). Hippocrates had observed the sudden and unexpected appearance of maternal grand-mal seizures, which occur when PE progresses to eclampsia, the word being derived from the Greek for ‘lightning’. It was believed for many centuries that PE was a seizure disorder unique to pregnancy, but during the last 200 years this view of the disease has changed drastically and we now know that it is not only a convulsive disorder. Several new findings have led to this change in opinion. At the turn of the last century, the new ability to measure blood pressure led to demonstration of the association of PE and hypertension (Cook & Briggs 1903); hypertension was often found to precede the development of eclamptic seizures. Young (1927) described placental damage that led to pregnancy-induced toxaemia. Later, the involvement of the kidneys was also observed since women who had died from eclampsia also had a unique form of glomerular endotheliosis (Bell 1932). These findings persuaded many to view the syndrome as a hypertensive rather than a seizure disorder (American College of Obstetricians and Gynecologists 1996). This change in classification unfortunately led many researchers to devote attention to the cause of the hypertension, to the exclusion of other facets of the disease (Roberts & Redman 1993). PE is now unanimously viewed as a multisystem disorder, as increases in blood pressure are rarely responsible for multi-organ dysfunction (Friedman et al. 1991). What is the array of complications associated with PE? In its latest document, the National Institutes of Health (2000) define mild PE as including an increase in blood pressure to greater than 140 mmHg systolic or 90 mmHg diastolic in a woman normotensive before her 20th week of pregnancy. Proteinuria is also present with a urinary excretion of at least 0·3 g protein in a 24 h specimen. Mild PE can develop directly into severe PE over a matter of days or weeks, this advancement being unpredictable in both its onset and its progression. There is a vast diversity of additional symptoms associated with this change (Patrick & Roberts 1999). These can include cerebral oedema (Cunningham & Twickler 2000), neurological manifestations (including headache, confusion, paralysis, coma, visual loss and seizures) (Royburt et al. 1991, Thomas 1998), liver capsule distension (Sheehan & Lynch 1973), renal failure (Lindheimer & Katz 1992), pulmonary oedema (Davison 1997), thrombocytopenia (Pritchard et al. 1987), coagulopathy (Barron et al. 1999), HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome (Weinstein 1982) and nausea (Martin et al. 1999). The primary cause of PE has been difficult to elucidate because its symptoms have always presented as a cluster of conditions. Several theories have been advocated and by far the most compelling evidence indicates that the placenta holds the key. The symptoms of PE disappear soon after birth or after pregnancy termination (Palma Gamiz 1998) when the placenta is no longer present. It is also apparent that the presence of a foetus is not necessary as some cases of hydatidiform mole, in which the uterus contains only disordered placental tissue, are complicated by the condition (Scott 1958). Finally, an utero–placental interaction is not required, as abdominal pregnancies can still encounter complications (Shembrey & Noble 1995). However, as PE affects only 5–10% of first pregnancies the presence of a placenta cannot be the sole cause. What then is different in the placentae of women prone to develop PE? Page (1939) first noted that placentae from these women appeared to be poorly perfused and today we know that a consistent feature associated with this poor perfusion is the defective trophoblast invasion of the myometrial portion of the spiral arteries (Pijnenborg et al. 1980, 1981). In normal pregnancy, trophoblast invasion of the spiral arteries renders them dilated, flaccid and unresponsive to vasoconstrictive agents (Brosens et al. 355

SummaryBetween 1 January and 31 December, 2006, 34 consecutive cases of severe pre-eclampsia (12), imminent eclampsia (10) and eclampsia (12) who were admitted at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife in the south-western part of Nigeria, were investigated for the development of HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome in a prospective study. The ages of the women ranged from 18 to 38 years, parity 0–5 and the estimated gestational age from 18–41 weeks at presentation. A total of 26 (76.5%) of the patients were unbooked, six (17.6%) of the 34 cases developed HELLP syndrome. Four (33%) of the 12 eclamptics developed HELLP syndrome, while only one (10%) of the cases of imminent eclampsia and 1 (8.3%) of severe pre-eclamptic cases developed the syndrome. Using the Mississippi Triple class system, none of the HELLP syndrome cases belonged to Class I; 4 were categorised in Class II while 2 were in Class III. All of the four eclamptic cases with HELLP syndrome died giving a 100% fatality rate while none of the imminent eclamptic and severe pre-eclamptic patients with the syndrome died. Furthermore, there were six (15.8%) perinatal deaths among the 38 infants delivered by the 34 mothers with severe pre-eclampsia/eclampsia. Our data suggest that the development of HELLP syndrome is more likely in eclamptic patients and when it occurs in them, it is highly fatal. Most of the cases in this study were unbooked. Substandard care may have contributed to the progression of the disease state and consequently, to maternal mortality. It is imperative to draw up an action plan for the identification of the risk factors for the development of pre-eclampsia/eclampsia at peripheral hospitals and maternity centres and for prompt referral of such cases afterwards. Efforts should also be geared towards the minimising of treatment delay in all phases, so as to minimise both perinatal and maternal morbidity and mortality.

Introduction: Pregnant women with chronic hypertension and who developed superimposed Preeclampsia (PE) had a higher rate of adverse maternal and perinatal outcomes. Prospective data on the outcome of pregnancies with chronic hypertension are sparse. Aim: To evaluate the maternal and perinatal outcomes in pregnancies complicated by chronic hypertension with and without superimposed PE in South Indian population. Materials and Methods: A two group, parallel, prospective observational study was carried out in 270 women with singleton pregnancy and chronic hypertension with and without superimposed PE and who received antenatal care and delivered in the Department of Obstetrics and Gynaecology at Fernandez hospital, Hyderabad, Telangana, India from March 2019 to February 2020. A total of 180 women had chronic hypertension without superimposed PE and 90 had superimposed PE (group A, 180 cases; group B, 90 cases). The medical records were reviewed with specific reference to the treatment, development of Foetal Growth Restriction (FGR), maternal and perinatal outcomes. FGR was considered as the primary outcome variable. Secondary variables were stillbirth rate, low birth weight, Neonatal Intensive Care Unit admissions, Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) at 5 minutes, gestational age at delivery, caesarean section rate and maternal complications. Categorical variables were assessed by Pearson’s Chi-square test. Continuous variables were assessed by unpaired student t-test. Results: The mean maternal age in group A was 32±5 years and in group B was 30±4 years. Adverse maternal outcomes like abruption, Haemolysis, Elevated liver enzymes, and Low platelets (HELLP) syndrome, and pulmonary oedema were all low in women without superimposed PE than those with superimposed PE (1.6% vs 12%, p≤0.001). There were no maternal deaths in either group. Compared to group A, group B showed higher FGR rate (15.5%vs 51.1%, p&lt;0.001), preterm deliveries (&lt;37 weeks) (50.5% vs 80% p&lt;0.001), stillbirths (0 vs 13.3%), low APGAR at 5 minutes (1.1% vs 16.6%%, p&lt;0.001), low birth weight (21.2% vs 71.1%, p&lt;0.001), NICU admissions (14.4% vs 43.3%, p&lt;0.001). There was no significant difference in the caeserean section rate between the groups (69.4% vs 74.4%, p=0.39). Conclusion: Maternal and perinatal morbidity was higher in women having chronic hypertension with superimposed PE. They need vigilant maternal and foetal surveillance and should be counseled about all the possible adverse outcomes.

BACKGROUND AND AIMS West Africa has among the highest levels of maternal and neonatal mortality and morbidity globally, including amongst conflict-affected populations. Many lives could be saved and much human suffering averted with effective implementation of low-cost, high impact interventions. METHODS UNHCR implemented a three-year Bill and Melinda Gates Foundation-funded project to reduce neonatal and maternal mortality and morbidity among 772,000 refugees in Cameroon, Chad and Niger. A mixed-method assessment identified needs and priorities. Action plans and a monitoring/supportive supervision tool were developed to track progress. Clinical training on leading causes of neonatal and maternal mortality were adapted using a low-dose, high-frequency approach. Health facilities were rehabilitated, equipped and supported with medicines and commodities, and job aids developed to enhance quality of care. Clinical activities linked with strong community outreach included home visits by community health workers during pregnancy and the first postnatal week. RESULTS A 25% reduction in neonatal mortality rate was achieved with 33,530 births (from 19.0 in Q4 2018 to 11.9/1,000 live births in 2021, p=0.02). Uptake of kangaroo mother care reached nearly 100% among newborns &lt; 2,000g. This, and improved clinical skills and availability of essential supplies, contributed to a decrease in neonatal mortality rates among low birth weight (LBW) newborns. Weighted case fatality rate for newborns with complications, and LBW newborns below 2000g decreased from 11.8% to 6.3%, and 31.5% to 12.3% respectively, from 2019 to 2021. CONCLUSIONS The combination of low-dose high-frequency trainings, health facility strengthening and community outreach activities improved neonatal outcomes and contributed towards sustainability. Future interventions among refugee populations should address persisting socio-cultural issues, including gender-related factors, affecting health access.

Global maternal and neonatal mortality rates remain unacceptably high. The postnatal period, encompassing the first hour of life until 42 days, is critical for mother-baby dyads, yet postnatal care (PNC) coverage is low. Identifying mother-baby dyads at increased risk for adverse outcomes is critical. Yet few efforts have synthesized research on proximate and distant factors associated with maternal and neonatal mortality during the postnatal period. This scoping review identified proximate and distant factors associated with maternal and neonatal mortality during the postnatal period within low- and middle-income countries (LMICs). A rigorous, systematic search of four electronic databases was undertaken to identify studies published within the last 11 years containing data on risk factors among nationally representative samples. Results were synthesized narratively. Seventy-nine studies were included. Five papers examined maternal mortality, one focused on maternal and neonatal mortality, and the rest focused on neonatal mortality. Regarding proximate factors, maternal age, parity, birth interval, birth order/rank, neonate sex, birth weight, multiple-gestation, previous history of child death, and lack of or inadequate antenatal care visits were associated with increased neonatal mortality risk. Distant factors for neonatal mortality included low levels of parental education, parental employment, rural residence, low household income, solid fuel use, and lack of clean water. This review identified risk factors that could be applied to identify mother-baby dyads with increased mortality risk for targeted PNC. Given risks inherent in pregnancy and childbirth, adverse outcomes can occur among dyads without obvious risk factors; providing timely PNC to all is critical. Efforts to reduce the prevalence of risk factors could improve maternal and newborn outcomes. Few studies exploring maternal mortality risk factors were available; investments in population-based studies to identify factors associated with maternal mortality are needed. Harmonizing categorization of factors (e.g., age, education) is a gap for future research.

Conflicts frequently occur in countries with high maternal and neonatal mortality and can aggravate difficulties accessing emergency care. No literature is available on whether the presence of conflict influences the outcomes of mothers and neonates during Caesarean sections (C-sections) in high-mortality settings. To determine whether the presence of conflict was associated with changes in maternal and neonatal mortality during C-sections. We analysed routinely collected data on C-sections from 17 Médecins Sans Frontières (MSF) health facilities in 12 countries. Exposure variables included presence and intensity of conflict, type of health facility and other types of access to emergency care. During 2008-2015, 30,921 C-sections were performed in MSF facilities; of which 55.4% were in areas of conflict. No differences were observed in maternal mortality in conflict settings (0.1%) vs. non-conflict settings (0.1%) (P = 0.08), nor in neonatal mortality between conflict (12.2%) and non-conflict settings (11.5%) (P = 0.1). Among the C-sections carried out in conflict settings, neonatal mortality was slightly higher in war zones compared to areas of minor conflict (P = 0.02); there was no difference in maternal mortality (P = 0.38). Maternal and neonatal mortality did not appear to be affected by the presence of conflict in a large number of MSF facilities. This finding should encourage humanitarian organisations to support C-sections in conflict settings to ensure access to quality maternity care.

Expectant management of severe preeclampsia at less than 27 weeks' gestation: maternal and perinatal outcomes according to gestational age by weeks at onset of expectant management

PP059. Angiogenic factors and risk of preeclampsia related adverse outcomes in twin pregnancies

BackgroundDespite considerable efforts to reduce the maternal mortality ratio, numerous pregnant women continue to die in many developing countries, including Nigeria. We conducted a study to determine the incidence and causes of maternal mortality over an 8-month period in a rural-based secondary health facility located in Jahun, northern Nigeria.MethodsA retrospective observational study was performed in a 41-bed obstetric ward. From October 2010 to May 2011, demographic data, obstetric characteristics, and outcome were collected from all pregnant women admitted. The total number of live births during the study period was recorded in order to calculate the maternal mortality ratio.ResultsThere were 2,177 deliveries and 39 maternal deaths during the study period, with a maternal mortality ratio of 1,791/100,000 live births. The most common causes of maternal mortality were hemorrhage (26%), puerperal sepsis (19%), and obstructed labor (5%). No significant difference (P = 0.07) in mean time to reach the hospital was noted between fatal cases (1.9 hours, 95% confidence interval [CI] 1.1–2.6) and nonfatal cases (1.4 hours, 95% CI 1.4–1.5). Two hundred and sixty-six women were admitted presenting with stillbirth. Maternal mortality was higher for unbooked patients than for booked patients (odds ratio 5.1, 95% CI 3.5–6.2, P < 0.0001). The neonatal mortality rate was calculated at 46/1,000 live births. The main primary causes of neonatal deaths were prematurity (44%) and birth asphyxia (22%).ConclusionMaternal and neonatal mortality remains unacceptably high in this setting. Reducing unbooked emergencies should be a priority with continuous programs including orthodox practices in order to meet the fifth Millennium Development Goal.

In August 1994, a 19-year-old woman presented to her dermatologist with a slight fever, arthralgia, and a butterfly rash. Discoid lupus erythematosus was suspected, and serological testing yielded positive results for antinuclear antibody. She was diagnosed with systemic lupus erythematosus without organ failure and was treated with only nonsteroidal antiinflammatory drugs. She became pregnant in June 2001, at age 26. In November her obstetrician noted that she had severe hypertension, edema of the low limbs, and proteinuria. On admission, she was diagnosed with severe preeclampsia, and cesarean section was performed. On hospital day 3 the patient developed sudden epigastric pain and vomiting. Laboratory tests revealed thrombocytopenia, liver dysfunction, and microangiopathic hemolytic anemia, leading to a diagnosis of HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Plasma exchange was performed for 5 days. The thrombocytopenia, liver dysfunction, and proteinuria diminished quickly. Later testing revealed a high titer of plasma phosphatidylserine-dependent anti-prothrombin antibody. This case is useful for exploring the relations between SLE, HELLP syndrome, and anti-prothrombin antibody.

The objective of this study was to examine first-trimester maternal serum placental growth factor (PlGF) levels in pregnancies which later develop hypertensive and growth complications. In this case-control study, PlGF levels were measured by AutoDELFIA immunoassay platform. There were 47 cases of at least one of the following adverse outcomes: pre-eclampsia (PE), small for gestational age (SGA), haemolysis elevated liver enzymes and low platelets (HELLP) and gestational hypertension (GH) and 452 matched controls. PlGF levels were significantly lower in cases of all PE, early PE, HELLP, all SGA, early SGA and SGA without PE, but not in GH, late PE, late SGA, PE with SGA or PE without SGA or HELLP. Low levels of first-trimester PlGF provide a good indicator of SGA complications and some hypertensive disorders, in particular severe cases of PE such as early onset and HELLP syndrome.

A case of atypical HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome presenting as bleeding from the epidural puncture site during labour

A randomised placebo-controlled trial of prolonged prednisolone administration to patients with HELLP syndrome remote from term