A case–control study of placental lesions associated with pre-eclampsia

ObjectiveTo investigate gross and microscopic placental lesions associated with pre-eclampsia and to determine which lesions are most strongly linked to serious pregnancy complications.MethodsA retrospective case–control study of 173 placentas from women with pre-eclampsia and 173 placentas from healthy normotensive women was conducted.ResultsThe mean placental weight in the pre-eclampsia group was lower than that recorded for the control group (280 g vs 360 g; P < 0.001). Infarcts (65.9% vs 13.2%; P < 0.001) and placental abruption (P < 0.001) were most frequent among women with pre-eclampsia. Microscopic findings showed the following lesions to be associated with pre-eclampsia: hypermature villi, defined by absence of intermediate villi (72% vs 16%; P < 0.001), excessive syncytial knots (90% vs 9%; P < 0.001), decidual vasculopathy (51% vs 8%; P < 0.001), villous fibrosis (6% vs 0%; P < 0.001), erythroblastosis (11% vs 4%; P < 0.01), and avascular terminal villi (9% vs 3%; P < 0.05). Increased syncytial knots, infarcts, basal decidual vasculopathy, hypermature villi, and placental erythroblastosis were still associated with pre-eclampsia after logistic regression modeling.ConclusionPlacental lesions most strongly associated with pre-eclampsia were all causes or expressions of placental hypoxia or ischemia, which appears as the primary mechanism of pre-eclampsia.     

Serum magnesium level in the first trimester of pregnancy as a predictor of pre-eclampsia – a pilot study

Objectives: The aim of this study was to evaluate the importance of serum concentration of magnesium (Mg) in the first trimester of pregnancy for predicting pre-eclampsia (PE). Methods: This prospective study included 403 pregnant women over 18, with singleton pregnancy (from 11 to 14 weeks of pregnancy). The subjects were divided into a group who subsequently developed PE (PEKT) (n = 61), and a group of healthy pregnancies with no complications and with normal outcomes (TNT) (n = 342). In the first trimester, urea, creatinine, uric acid, Mg, free beta subunit of human chorionic gonadotrophin, plasma protein A related to pregnancy, and C-reactive protein were determined. We followed all subjects until the end of pregnancy. Results: Serum Mg is significantly lower in PEKT than in TNT group (p < 0.001). The serum first trimester Mg level cutoff at ≤0.81 mmol/L had a sensitivity of 77.0% and specificity of 71.6% for the detection of women with PEKT. The level of serum Mg has the strongest significant positive correlation (p < 0.05) with the week of gestational outcomes (R = 0.442), weight (R = 0.416), and Apgar score (R = 0.343) of the newborns, and the strongest significant negative correlation with the number of miscarriages (R = ?0.413), serum creatinine (R = ?0.471), and the number of pregnancies (R = ?0.326). The week of gestational outcome is predicted with the greatest reliability by the serum Mg. Conclusions: Serum Mg level during the first trimester of pregnancy is a significant prediction tool for PE and could also play an important role in predicting the week of gestational outcome and birth weight of newborns.     

Placental growth factor,vascular endothelial growth factor,and hypoxia-inducible factor-1α in the placentas of women with pre-eclampsia

Background: Although the exact mechanism of pre-eclampsia – high blood pressure and proteinuria after 20 gestational weeks – is not yet fully understood, placental growth factor (PLGF), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor (HIF) are known to play important roles in vascularization and in the pathology of pre-eclampsia.

Methods: PLGF, VEGF, and HIF-1α were evaluated by immunohistochemistry in the placentas of Sudanese women with mild or severe pre-eclampsia, and in normal controls.

Results: Sixty-two women had severe pre-eclampsia, 102 had mild pre-eclampsia and 101 women served as healthy controls. Immunohistochemical staining of PLGF was significantly lower in placentas of women with severe pre-eclampsia (16%) compared with those with mild pre-eclampsia (8.8%) and placentas of normotensive women (40.6%; p?p?=?.020) of the placentas of women with severe or mild pre-eclampsia and in controls, respectively. Significantly more of the pre-eclamptic placentas expressed HIF-1α: in 15%, 10.8%, and 5.0% of the placentas of women with severe or mild pre-eclampsia, and in controls, respectively (p?=?.044).

Conclusion: The current study showed that PLGF, VEGF, and HIF-1α are involved in the pathophysiology of pre-eclampsia.     

Transforming growth factor beta-1 (TGF-β1) gene single nucleotide polymorphisms (SNPs) and susceptibility to pre-eclampsia in Iranian women: A case–control study

ObjectivesPre-eclampsia (PE) is a disorder of pregnancy characterized by high blood pressure and proteinuria. Transforming growth factor beta-1 (TGF-β1) is an important replicated PE candidate gene, and few studies have evaluated the direct association of TGF-β polymorphisms and risk to PE. The aim of this study was to investigate the association between three SNPs of TGF-β1 and serum level of this cytokine in PE patients and controls.Design and methodsIn this study the polymorphisms of the TGF-β1 gene at the coding region, and positions 29T→C (Leu 10 Pro), 74G→C (Arg 25 Pro) and 788C→T (Thr 263 Ile) were studied in 123 PE and 120 normal subjects using PCR-restriction fragment length polymorphism PCR-(RFLP) and amplification refractory mutation system (ARMS)-PCR methods. Moreover, serum TGF-β1 was determined by enzyme-linked immunosorbent assay (ELISA) technique.ResultsAt positions 74G→C and 29T→C the genotypes and allele frequencies showed no significant differences between PE patients and normal controls (P = 0.3 and P = 0.5 respectively). While in the case of position 788C→T both genotypes and allele frequencies were significantly different between PE patients and controls (P = 0.02). Haplotype analysis on three polymorphic sites showed no significant differences between PE and control individuals (P = 0.8). TGC and CGC haplotypes were the most frequent in both studied groups. The mean serum TGF-β1 level was significantly higher (62.73 ng/ml) in PE patients compared with pregnant (47.01 ng/ml) and non-pregnant (40.68 ng/ml) control groups (P = 0.0001).ConclusionsThe results of this study suggest that TGF-β1 gene 788C→T polymorphism is an important factor mediating the casual pathway of preeclampsia.     

Relation between first trimester maternal serum leptin levels and body mass index in normotensive and pre-eclamptic pregnancies – Role of leptin as a marker of pre-eclampsia: A prospective case–control study

Objective.?We measured first trimester plasma leptin concentrations in 37 women who subsequently developed pre-eclampsia and 53 normotensive controls to determine the interrelation between leptin and body mass index (BMI) in both groups. We further investigated the association between the risks for pre-eclampsia with maternal leptin levels.

Methods.?Bloods samples were collected at 13 weeks. Non-parametric tests, Spearman's correlation, linear regression analysis and multiple logistic regression analysis were applied in our data.

Results.?1?kg/m² increase in pre-pregnancy BMI was related to a 2.747 (95% CI: 3.242–2.252) ng/ml rise in leptin concentration among cases and 2.502 (95% CI: 2.873–2.131) ng/ml rise in leptin concentrations among controls. Increased leptin concentration (≥25.3?ng/ml ) in lean women is associated with a 18.8-fold increased risk of pre-eclampsia (adjusted OR: 18.8, CI: 1.8–194, p?=?0.014 ). Leptin treated as a continuous variable is a significant predictor of pre-eclampsia (adjusted OR: 1.08, CI: 1.018–1.133, p?=?0.009).

Conclusion.?Increased leptin concentration can definitely contribute to the prediction of pre-eclampsia in lean women, but this is not the case in overweight women. Further research in terms of longitudinal case–control studies is required to clarify the predictive value of pre-eclampsia.     

Pathology findings in preterm placentas of women with autoantibodies: a case–control study

Objective: To evaluate the placental histopathology findings in women with systemic lupus erythematosus or antiphospholipid syndrome delivered preterm. Methods: We performed a case-control study comparing clinical outcomes and placental histopathology of 18 consecutive singleton pregnancies with systemic lupus erythematosus (n = 9) or antiphospholipid syndrome (n = 9) delivered between 24 and 37 weeks, and 54 controls matched for gestational age and type of preterm delivery (spontaneous or indicated). Placental examinations were performed by a single pathologist, and placental lesions were grouped into four categories: uteroplacental vascular pathology and related villous lesions; coagulation-related damage; chronic inflammation; and acute inflammatory lesions. Statistical analysis included the Mantel-Haenzsel or Fisher's exact test, and logistic regression, with a value of p < 0.05 or an odds ratio (OR) with 95% confidence intervals (CI) not inclusive of unity considered significant. Results: Lupus anticoagulant was positive in ten out of 18 cases and medium or high positive IgG anticardiolipin antibodies in seven out of 18. Antenatal treatment included corticosteroids (n = 9), low-dose aspirin (n = 15) and heparin (n = 8). Rates of necrotizing enterocolitis (33% vs. 0%, p < 0.001) and of perinatal mortality (33% vs. 9%, p = 0.02) were significantly different between cases and controls, and rates of birth weight < 10th centile approached statistical significance. Uteroplacental vascular lesions (OR 3.7, 95% CI 1.1, 11.7) and coagulation-related damage (OR 16.8, 95% CI 3.9, 72.6) were significantly more common among cases than controls, and rates of chronic inflammatory lesions approached significance. Conclusions: Cases of systemic lupus erythematosus and antiphospholipid syndrome delivered preterm are associated with a significant increase in placental vascular and coagulation-related lesions, which are reflected clinically by higher rates of perinatal mortality, necrotizing enterocolitis, and small-for-gestational age neonates.     

Decreased placental thickness and impaired Doppler indices in idiopathic polyhydramnios: a prospective case–control study

Objective: To evaluate placental thickness, Doppler velocimetry, biophysical profile and perinatal outcomes in pregnancies complicated by idiopathic polyhydramnios.

Materials and methods: This prospective case–control study was conducted on 139 pregnant women, of these 70 patients with idiopathic polyhydramnios comprised the study group and 60 pregnant women comprised the control group. Risk factors recorded were; age, parity, body mass index (BMI), gestational weeks, amniotic fluid index (AFI), biophysical profiles (BPP), placental thickness, middle cerebral artery pulsatility index (MCA PI), umbilical artery Doppler velocimetry (Umb A S/D) values and perinatal outcomes.

Results: Sixty-nine of the cases had mild-moderate (AFI: 250–450?mm) polyhydramnios (%98.5) and one of the cases had severe polyhydramnios (>450?mm) in study group. There was no statistically significant difference between the groups in terms of age, parity, BMI, gestational weeks, fetal birth weights and BPP (p?>?0.05). Placental thickness, MCA PI and UA S/D values showed statistically significant difference between the groups (p?<?0.05). The fetuses with lower placental thickness had lower scores of biophysical profile. There were negative correlations between placental thickness and AFI (r?=??0.265), umbilical artery S/D and placental thickness (r?=??0.212), MCA PI and AFI (r?=??171, p?=?0.44). However there was a positive correlation between AFI and umbilical artery Doppler values (r?=?0.450).

Conclusion: Idiopathic polyhydramnios is associated with decreased placental thickness, impaired uterine, umbilical and middle cerebral artery flow.     

Is serum placental growth factor more effective as a biomarker in predicting early onset preeclampsia in early second trimester than in first trimester of pregnancy?

Purpose

To determine whether maternal serum placental growth factor (PlGF) is more effective as a biomarker in predicting the occurrence of early onset preeclampsia in first trimester or early second trimester of pregnancy.

Methods

A prospective cohort study was conducted on women with singleton pregnancies, screened from the antenatal clinic. Serum PlGF estimation was done at 11–14 weeks of gestation on 1,244 women and at 22–24 weeks of gestation on 1,206 women from the initial study population. A cut-off value of <228 pg/ml for serum PlGF at 11–14 weeks of gestation and <144 pg/ml for serum PlGF at 22–24 weeks of gestation were determined by receiver operating characteristic (ROC) curve analysis for identifying pregnant women at risk of developing early onset preeclampsia (<32 weeks of gestation). Univariate logistic regression analysis was used to analyze the association between serum PlGF < 228 pg/ml at 11–14 weeks of gestation and <144 pg/ml at 22–24 weeks of gestation with the occurrence of early onset preeclampsia and odds ratio (OR) was computed. P value < 0.05 was considered statistically significant in this study.

Results

Maternal serum PlGF <144 pg/ml at 22–24 weeks of gestation had a stronger association (OR 18.83; 95 % CI 12.08–22.24; p = 0.000) than serum PlGF <228 pg/ml at 11–14 weeks of gestation (OR 2.76; 95 % CI 1.29–3.94; p = 0.007) with the occurrence of early onset preeclampsia. The sensitivity and specificity of serum PlGF <144 pg/ml at 22–24 weeks of gestation (84 and 78, respectively) were much higher than those of serum PlGF <228 pg/ml at 11–14 weeks of gestation (58 and 66, respectively) in predicting early onset preeclampsia.

Conclusion

Maternal serum PlGF may be more effective as a biomarker in early second trimester than in first trimester of pregnancy, in predicting the occurrence of early onset preeclampsia.     

Ovarian reserve in young women with low birth weight and normal puberty: a pilot case–control study

Aim.?Studies indicate that women born small for gestational age (SGA) have impaired ovarian function. The origin of this ovarian dysfunction is still debatable. The aim of this study was to compare ovarian ageing between girls born appropriate for gestational age (AGA) and SGA. Therefore, we measured Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), E2, Anti-Müllerian hormone (AMH) levels and the pituitary response to endogenous Gonadotropin-releasing hormone (GnRH) in adolescent girls born SGA and AGA.

Methods.?A case–controlled pilot study consisting of seven SGA women (birth weight?<10th percentile AGA) and 13 AGA women with regular menstrual cycles, age 19.9 (±0.42). Early follicular FSH, LH, Oestradiol (E2) and AMH levels were measured. After baseline samples, 100?μg GnRH was administered intravenously and at 30, 60 and 90?min blood samples were taken to measure gonadotropin levels and to compute the response to endogenous GnRH.

Results.?Mean follicular phase LH, FSH, E2 and AMH levels did not significantly differ between young women born SGA and AGA. Furthermore, the response to endogenous GnRH showed no significant differences either.

Conclusions.?We concluded against extension of this pilot study. Based on our observations it seems unlikely that limited ovarian reserve is a predominated problem in adolescent SGA.     

Preeclampsia and depression: a case–control study in Tehran

Purpose

This study was conducted to determine the correlation between preeclampsia and depression.

Methods

Participants in this study included 156 cases with preeclampsia and 156 controls without any history of preeclampsia who were all newly admitted to antepartum wards, emergency room wards, and labor and delivery wards of the study hospitals (Valieasr, Shariatti, Mirza Koochak Khan, Shahid Akbar Abadi, Baharloo and Arash). They consented and completed a questionnaire on demographic characteristics, obstetric, delivery and infant information and Patient Health Questionnaire (PHQ-9) to assess their depression status. Data were analyzed through independent t test, Mann–Whitney U test, Chi-squared test, Fisher’s exact test and multiple regression by SPSS and STATA.

Results

Moderate to severe depression was found in 31.2% of the cases and 24.8% of the controls. Women with no depression in comparison with women with mild depression had a 1.81-fold (95% CI 1.05–3.14; P = 0.03) increased risk of preeclampsia, while moderate to severe depression correlated with a 2.52-fold increase (95% CI 1.05–6.02; P = 0.03) after adjustment of the probable confounding variables.

Discussion

With regard to the high prevalence of moderate to severe depression and its association with preeclampsia, our findings support and suggest efforts for screening depression among pregnant women and appropriate educational studies for mental and psychological problems during pregnancy.     

Association of interleukin-6 in women with persistence of DNA-HPV: a nested case–control study

Objective  

To identify the role of Interleukin-6, IL-10 and their epidemiological association in women with persistence of DNA-HPV.     

Clinical characteristics, metabolic features, and phenotype of Chinese women with polycystic ovary syndrome: a large-scale case–control study

Aim

The Rotterdam criteria extend the phenotypic spectrum of polycystic ovary syndrome (PCOS). The study was to investigate the clinical and biochemical features of a large-scale clinic based on the samples of Chinese women and to evaluate the value of Rotterdam criteria on Chinese PCOS women.

Methods

One thousand four hundred and four Chinese women were involved in our study, among whom, 719 cases were diagnosed as PCOS based on 2003 Rotterdam criteria, and 685 women without history of hyperandrogenism and with regular menstrual cycles were recruited as control. Clinical features, ultrasonographic (ovarian follicle number and volume), hormonal and metabolic parameters were commenced as outcome measures.

Results

Among 719 PCOS women, 6.1 % had hirsutism, 13.3 % had acne, 21.1 % had hyperandrogenism, 94.2 % had polycystic ovaries on ultrasonographic examination, and 88.6 % had menstrual abnormality. About one-third of the total PCOS patients were insulin resistant. The most frequent PCOS phenotype is the non-hyperandrogenic phenotype (O + P). Total testosterone, LH/FSH ratio, body mass index (BMI), and Ferriman and Gallwey scores (F–G) were all significantly higher in PCOS groups compared with non-PCOS group. Women with PCOS and obesity had higher serum testosterone, fasting insulin, longer menstrual cycle and larger ovarian follicle number, and LH/FSH ratio, estradiol or ovarian volume were similar between obese and normal BMI women. The LH level was statistically lower in the obese PCOS group.

Conclusions

Rotterdam criteria are generally applicable to Chinese population. Chinese women with PCOS showed lower rates of hyperandrogenemia, hirsutism, obesity, and insulin resistance. Obesity aggravates menstrual irregularity and increases the follicle number and serum total testosterone level.     

Maternal characteristics and birth outcomes of pregnant women who had offspring with congenital ear abnormalities – a population-based case–control study

Objective.?To describe the maternal characteristics and birth outcomes of newborn infants affected with isolated ear congenital abnormalities (IECA), mainly isolated anotia/microtia and unclassified multiple congenital abnormalities (CAs) including anotia/microtia (UMAM).

Method.?Cases with IECA and UMAM were compared with their matched controls and all controls without any defect and malformed controls affected with other defects in the population-based large dataset of the Hungarian Case–Control Surveillance of Congenital Abnormalities.

Results.?The mothers of 354 cases with IECA did not show significant difference in age, but their mean birth order was higher while their socio-economic status based on the maternal employment status was lower compared to the figures of their matched controls. There was a male excess among cases with microtia and mainly with UMAM. The evaluation of birth outcomes of newborns affected with IECA indicated intrauterine fetal growth retardation.

Conclusions.?Newborn infants with isolated microtia had intrauterine growth retardation and the association of this developmental defect localized for a small region of head with the general fetal development raises interesting theoretical question.     

Anti muellerian hormone serum levels in women with endometriosis: A case–control study

Objective.?To compare the anti muellerian hormone (AMH) serum levels in women with and without endometriosis.

Design.?A case–control study

Setting.?Women's General Hospital, Linz, Austria.

Patient(s).?Our study included a total of 909 patients undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment or consulting our specific endometriosis unit. After proofing the exclusion criteria, 153 of these patients with endometriosis (study group) were matched with 306 patients undergoing IVF/ICSI treatment because of a male factor (control group).

Interventions.?None.

Main outcome measures.?AMH serum level.

Results.?Mean AMH serum level was significantly lower in the study than in the control group (2.75?±?2.0?ng/ml vs. 3.46?±?2.30?ng/ml, p?<?0.001). In women with mild endometriosis (rAFS I-II), the mean AMH level was almost equal to the control group (3.28?±?1.93?ng/ml vs. 3.44?±?2.06?ng/ml; p?=?0.61). A significant difference in mean AMH serum level was found between women with severe endometriosis (rAFS III-IV) and the control group (2.38?±?1.83?ng/ml vs. 3.58?±?2.46?ng/ml; p?<?0.0001).

Conclusion.?Lower AMH serum levels and an association with the severity were found in women with endometriosis. Physicians have to be aware of this fact. Because of the expected lower response on a controlled ovarian hyperstimulation (COH), AMH serum level should be measured to optimise the dose of gonadotropin treatment previous to a COH, especially in women with severe endometriosis.     

Possible association between hyperthyroidism in pregnant women and obstructive congenital abnormalities of urinary tract in their offspring – a population-based case–control study

Objective.?The teratogenic potential of some antithyroid drugs is known, but the aim of the study was to estimate the risk of congenital abnormalities (CAs) in the offspring of pregnant women with hyperthyroidism with or without antithyroid drug treatment.

Method.?Comparison of the occurrence of medically recorded hyperthyroidism who had malformed fetuses/newborns (cases) and who delivered healthy babies (controls) in the population-based Hungarian Case–Control Surveillance System of CAs, 1980–1996. Of 22,843 cases with congenital abnormalities, 71 (0.31%) while of 38,151 controls, 116 (0.30%) had mothers with hyperthyroidism. The rate of hyperthyroidism in the mothers of cases with different CAs and in the mothers of matched controls was compared.

Results.?Preeclampsia–eclampsia occurred more frequently in pregnant women with hyperthyroidism without antithyroid treatment. The analysis of specific groups of CAs showed an association between hyperthyroidism in pregnant women and obstructive defects of urinary tract in their children.

Conclusions.?The lack of appropriate treatment of pregnant women affected with hyperthyroidism seems to be the major problem, because it would be necessary to prevent the hyperthyroidism related risks of pregnancy complications and CAs which exceed the risk of antithyroid medication in these pregnant women.     

Pregnancy complications in the mothers who delivered boys with isolated hypospadias – a population-based case–control study

Objective: The evaluation of pregnancy complications of mothers who delivered boys with isolated hypospadias (IHS) to estimate their roles in the higher rate of low birthweight and preterm birth in cases with IHS.

Methods: The incidence of prospectively and medically recorded pregnancy complications in the prenatal maternity logbook was compared in the mothers of 3038 cases with IHS and their 4981 matched controls, in addition, 24?814 population male controls without any defects in the Hungarian Case–Control Surveillance of Congenital Abnormalities, 1980–1996.

Results: The well-known higher rate of preterm birth and mainly of low birthweight was confirmed in cases with IHS. The incidence of preeclampsia/eclampsia (OR with 95% CI: 1.92, 1.62–2.27) and gestational diabetes (1.94, 1.34–2.81) was higher, while severe nausea and vomiting in pregnancy (0.77, 0.66–0.88) showed a lower incidence in the mothers of cases.

Conclusion: The higher rate of preeclampsia/eclampsia may have a role in the intrauterine growth restriction of fetuses affected with IHS while the lower rate of nausea and vomiting in pregnancy may associate with the higher risk of preterm birth.     

Oxidative stress in preeclamptic mother – newborn dyads and its correlation with early neonatal outcome – a case control study

Background: Preeclamptic mothers are likely to have increased oxidative stress during pregnancy which can adversely affect the outcome in their neonates.

Objectives: To measure the oxidative stress in preeclamptic mother- newborn dyads and correlate it with the immediate neonatal outcome.

Methods: This case control study conducted in a tertiary care teaching hospital, South India included 71 preeclamptic mothers – newborn dyads (cases) and 72 normal mothers – newborn dyads (controls). Biochemical parameters including total antioxidant status (TAS), protein carbonyls and malondialdehyde levels (MDA) were measured in both maternal and cord blood. Association between these oxidative stress parameters and early neonatal outcome was studied.

Results: All oxidative stress markers were higher in the preeclampsia group compared to the controls. Cord blood protein carbonyl levels had significant correlation with maternal levels. Prematurity, low-birth weight, respiratory distress syndrome (RDS), early onset sepsis (EOS) and intra-uterine growth restriction (IUGR) were more among cases. Early neonatal outcomes like death, IUGR, EOS, and RDS had significant correlation with protein carbonyl levels among the cases.

Conclusions: Oxidative stress is increased in preeclamptic mother – newborn dyads. Increased protein carbonyl levels in preeclampsia correlate with adverse early neonatal outcome.     

Obstetric and neonatal outcomes in a home-like birth centre: a case–control study

Purpose

To compare the intervention rates associated with labor in low-risk women who began their labor in the “home-like birth centre” (HLBC) and the traditional labor ward (TLW).

Methods

This retrospective study used data that were collected from January 2005 to June 2008, from women admitted to the HLBC (n = 316) and compared to a group of randomly selected low-risk women admitted to the TLW (n = 890) using the Baysian information criterion to select the best predictive model.

Results

Women in the HLBC had spontaneous vaginal deliveries more often (88.6 vs. 82.8 %, p value 0.034) and perineal lesions less often (60.1 vs. 62.5 %, p value 0.013). The frequency of adverse neonatal outcomes did not differ statistically between the two groups, although the mean clamped at birth umbilical arterial pH level was higher in the HLBC group. The transfer rate from HLBC to TLW was 31.3 % of which 75.8 % were nulliparae.

Conclusions

It appears that women could benefit from HLBC care in settings such as the one studied. Larger observational studies are warranted to validate these results.