Preeclampsia at delivery is associated with lower serum vitamin D and higher antiangiogenic factors: a case control study.

BACKGROUND: Preeclampsia is characterized by decreased trophoblastic angiogenesis leading to abnormal invasion of spiral arteries, shallow implantation and resulting in compromised placentation with poor uteroplacental perfusion. Vitamin D plays an important role in pregnancy influencing implantation, angiogenesis and placental development. The objective of this study was to determine whether there is an association between serum vitamin D levels, and anti-angiogenic factors at the time of delivery and the occurrence of preeclampsia. METHODS: This nested case control study analyzed frozen serum samples at the time of delivery and related clinical data from women with singleton liveborn pregnancies who had participated in studies of the NICHD Stillbirth Collaborative Research Network. Women with a recorded finding of preeclampsia and who had received magnesium sulfate treatment prior to delivery were considered index cases (N = 56). Women without a finding of preeclampsia were controls (N = 341). RESULTS: Women with preeclampsia had 14.5% lower serum vitamin D levels than women in the control group (16.5 ng/ml vs. 19 ng/ml, p = 0.014) with 64.5% higher sFlt-1 levels (11,600 pg/ml vs. 7050 pg/ml, p < 0.001) and greater than 2 times higher endoglin levels (18.6 ng/ml vs. 8.7 ng/ml, < 0.001). After controlling for gestational age at delivery and maternal BMI, vitamin D levels were 0.88 times lower (P = 0.051), while endoglin levels were 2.5 times higher and sFlt-1 levels were 2.1 times higher than in control pregnancies (P < 0.001). CONCLUSIONS: Women with preeclampsia at time of delivery have higher maternal antiangiogenetic factors and may have lower maternal serum vitamin D levels. These findings may lead to a better understanding of the underlying etiology of preeclampsia as well as possible modifiable treatment options which could include assuring adequate levels of maternal serum vitamin D prior to pregnancy.

Maternal Marijuana Exposure, Feto-Placental Weight Ratio, and Placental Histology.

OBJECTIVE: Marijuana use is associated with placenta-mediated adverse pregnancy outcomes including fetal growth restriction, but the mechanism remains uncertain. The objective was to evaluate the association between maternal marijuana use and the feto-placental weight ratio (FPR). Secondarily, we aimed to compare placental histology of women who used marijuana to those who did not. STUDY DESIGN: This was a secondary analysis of singleton pregnancies enrolled in a multicenter and case-control stillbirth study. Prior marijuana use was detected by electronic medical record abstraction or cord homogenate positive for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. Prior tobacco use was detected by self-report or presence of maternal serum cotinine. Stillbirths and live births were considered separately. The primary outcome was FPR. Association of marijuana use with FPR was estimated with multivariable linear modeling adjusted for fetal sex, preterm birth, and tobacco use. Comparisons between groups for placental histology were made using Chi-square and stratified by live birth and stillbirth, term and preterm deliveries, and fetal sex. RESULTS: Of 1,027 participants, 224 were stillbirths and 803 were live births. Overall, 41 (4%) women used marijuana during the pregnancy. The FPR ratio was lower among exposed offspring but reached statistical significance only for term stillbirths (mean 6.84 with marijuana use vs. mean 7.8 without use, p < 0.001). In multivariable modeling, marijuana use was not significantly associated with FPR (p = 0.09). There were no differences in histologic placental features among those with and without marijuana use overall or in stratified analyses. CONCLUSION: Exposure to marijuana may not be associated with FPR. Similarly, there were no placental histologic features associated with marijuana exposure. Further study of the influence of maternal marijuana use on placental development and function is warranted to better understand the association between prenatal marijuana use and poor fetal growth. KEY POINTS: · Maternal marijuana exposure was not associated with the feto-placental weight ratio.. · Marijuana exposure was not associated with differences in placental histology.. · Concerning trend toward lower feto-placental weight ratios among marijuana-exposed stillbirths..

Perceptions of women, their husbands and healthcare providers about anemia in rural Pakistan: Findings from a qualitative exploratory study.

BACKGROUND: In Pakistan, there is a dearth of literature on the perceptions of anemia among women of reproductive age (WRA). This study was undertaken to explore the perceptions of women, their husbands, and healthcare providers about anemia, its possible causes, and how anemia impacts maternal and child health in Thatta, Pakistan. METHODS: A qualitative study was conducted in Thatta, Pakistan from September to December 2018. Using a pre-tested semi-structured interview (SSI), we collected data to understand their definitions of anemia through ten focus group discussions (FGDs) with women and their partners and ten primary informant interviews (KIIs) with healthcare providers. We identified six major themes: (I) Knowledge and awareness of anemia, (II) Causes and consequences of Anemia, (III) Dietary practices, (IV) Knowledge and practices regarding the use of iron-folic acid supplements, (V) Factors influencing prevention and control of anemia and (VI) Women's health behavior. We analyzed the data through thematic analysis using NVivo 10 software. RESULTS: Most community members were not aware of the term anemia but described anemia as a condition characterized by 'blood deficiency' in the body. All study participants perceived anemia as an important health problem tending to cause adverse outcomes among WRA and their children. Study participants perceived gutka (chewable tobacco) consumption as an important cause of anemia. Healthcare providers identified short inter-pregnancy intervals, lack of family planning, poor health-seeking behavior, and consumption of unhealthy food as causes of anemia in the district. Consumption of unhealthy food might not be related to related to a poorer knowledge of iron-deficient foods, but economic constraints. This was further endorsed by the healthcare providers who mentioned that most women were too poor to afford iron-rich foods. All men and women were generally well versed with the sources of good nutrition to be consumed by WRA to prevent anemia. CONCLUSION: The findings suggest that the government should plan to develop strategies for poverty-stricken and vulnerable rural women and plan health awareness programs to improve dietary practices, compliance with supplements, and health-seeking behavior among women of reproductive age. There is a need to develop effective counseling strategies and context-specific health education sessions to improve the health-seeking behavior of women and men in the Thatta district of Pakistan. Besides, there is need to address social determinants of health such as poverty that pushes women of poorer socioeconomic strata to eat less nutritious foods and have more anaemia. Therefore, a comprehensive and robust strategic plan need to be adopted by government that focuses not only on the awareness programs, but also aim to reduce inequities that lead to pregnant women eat iron-poor foods, which, in turn, forces them to become anemic.

Use of Smokeless Tobacco Before Conception and Its Relationship With Maternal and Fetal Outcomes of Pregnancy in Thatta, Pakistan: Findings From Women First Study.

INTRODUCTION: Smokeless tobacco (SLT) consumption during pregnancy has adverse consequences for the mother and fetus. We aimed to investigate the effects of maternal pre-pregnancy SLT consumption on maternal and fetal outcomes in the district of Thatta, Pakistan. AIMS AND METHODS: We conducted a secondary data analysis of an individual randomized controlled trial of preconception maternal nutrition. Study participants were women of reproductive age (WRA) residing in the district of Thatta, Pakistan. Participants were asked questions regarding the usage of commonly consumed SLT known as gutka (exposure variable). Study outcomes included maternal anemia, miscarriage, preterm births, stillbirths, and low birth weight. We performed a cox-regression analysis by controlling for confounders such as maternal age, education, parity, working status, body mass index, and geographic clusters. RESULTS: The study revealed that 71.5% of the women reported using gutka, with a higher proportion residing in rural areas as compared with urban areas in the district of Thatta, Pakistan. In the multivariable analysis, we did not find a statistically significant association between gutka usage and anemia [(relative risk, RR: 1.04, 95% confidence interval, CI (0.92 to 1.16)], miscarriage [(RR: 1.08, 95% CI (0.75 to 1.54)], preterm birth [(RR: 1.37, 95% CI (0.64 to 2.93)], stillbirth [(RR: 1.02, 95% CI (0.39 to 2.61)], and low birth weight [(RR: 0.96, 95% CI (0.72 to 1.28)]. CONCLUSIONS: The study did not find an association between gutka usage before pregnancy and adverse maternal and fetal outcomes. In the future, robust epidemiological studies are required to detect true differences with a dose-response relationship between gutka usage both before and during pregnancy and adverse fetomaternal outcomes. IMPLICATIONS: While most epidemiological studies conducted in Pakistan have focused on smoking and its adverse outcomes among males, none of the studies have measured the burden of SLT among WRA and its associated adverse outcomes. In addition, previously conducted studies have primarily assessed the effect of SLT usage during pregnancy rather than before pregnancy on adverse fetal and maternal outcomes. The current study is unique because it provides an insight into the usage of SLT among WRA before pregnancy and investigates the association between pre-pregnancy SLT usage and its adverse fetomaternal outcomes in rural Pakistan.

Cytokine profiling: variation in immune modulation with preterm birth vs. uncomplicated term birth identifies pivotal signals in pathogenesis of preterm birth.

OBJECTIVES: To assess deviations in longitudinally measured cytokines with preterm birth (PTB). METHODS: Prospective longitudinal study targeting 80 subjects. Phlebotomy specimens for broad panel of cytokine analysis were obtained at three time (T) intervals: first trimester (T1: 8-14 weeks' gestation), second trimester (T2: 18-22 weeks' gestation), and third trimester (T3: 28-32 weeks' gestation). Important demographics and outcomes were tracked. Data were stratified and the target groups were analyzed as follows: "Uncomplicated" (delivered ≥37 weeks) or "Preterm Birth" (<37 weeks). Generalized Linear Modeling determined rate of change T1-T3 by outcome. RESULTS: Complete data replete with phlebotomy at all three visits were obtained on 80 women. Birth outcomes were as follows: 11 Uncomplicated Term Birth (UTB), 28 PTB, 4 low birth weight (LBW), 16 OB complications (OBC), 11 current infections (IFN), and 10 mixed complications (MC=2 or more of the above). 28 PTB were compared to 11 uncomplicated term deliveries. In both groups, T helper type 1 (TH1) cytokine (IL-1ß), pleiotrophic pro-inflammatory cytokine (IL-6), and counter-regulatory cytokine (IL-10) responses decreased over gestation, but rates of change in IL-1ß, IL-6, and IL-10 were significantly different. Stratification of women by smoking status additionally demonstrated significant variance in immune status over the course of pregnancy. CONCLUSIONS: Women delivering PTB demonstrated significant differences in cytokine trajectory over pregnancy; these data further validate key role played by immune regulation in directing pregnancy outcome. Likewise, smoking impacts longitudinal trajectory of cytokines over pregnancy.

A comparison of MITS counseling and informed consent processes in Pakistan, India, Bangladesh, Kenya, and Ethiopia.

Globally, more than 5 million stillbirths and neonatal deaths occur annually. For many, the cause of death (CoD) is unknown. Minimally invasive tissue sampling (MITS) has been increasingly used in postmortem examinations for ascertaining the CoD in stillbirths and neonates. Our study compared the counseling and consent methods used in MITS projects in five countries in Africa and south Asia. Key informant interviews were conducted with researchers to describe the characteristics and backgrounds of counselors, the environment and timing of consent and perceived facilitators and barriers encountered during the consent process. Counselors at all sites had backgrounds in social science, psychology and counseling or clinical expertise in obstetrics/gynecology or pediatrics. All counsellors received training about techniques for building rapport and offering emotional support to families; training duration and methods differed across sites. Counselling environments varied significantly; some sites allocated a separate room, others counselled families at the bedside or nursing stations. All counsellors had a central role in explaining the MITS procedure to families in their local languages. Most sites did not use visual aids during the process, relying solely on verbal descriptions. In most sites, parents were approached within one hour of death. The time needed for decision making by families varied from a few minutes to 24 h. In most sites, extended family took part in the decision making. Because many parents wanted burial as soon as possible, counsellors ensured that MITS would be conducted promptly after receiving consent. Barriers to consent included decreased comprehension of information due to the emotional and psychological impact of grief. Moreover, having more family members engaged in decision-making increased the complexity of counselling and achieving consensus to consent for the procedure. While each site adapted their approach to fit the context, consistencies and similarities across sites were observed.

The association of stillbirth with placental abnormalities in growth-restricted and normally grown fetuses.

BACKGROUND: Stillbirth, defined as foetal death ≥20 weeks' gestation, is associated with poor foetal growth and is often attributed to placental abnormalities, which are also associated with poor foetal growth. Evaluating inter-relationships between placental abnormalities, poor foetal growth, and stillbirth may improve our understanding of the underlying mechanisms for some causes of stillbirth. OBJECTIVE: Our primary objective was to determine whether poor foetal growth, operationalised as small for gestational age (SGA), mediates the relationship between placental abnormalities and stillbirth. METHODS: We used data from the Stillbirth Collaborative Research Network study, a population-based case-control study conducted from 2006-2008. Our analysis included 266 stillbirths and 1135 livebirths. We evaluated associations of stillbirth with five types of placental characteristics (developmental disorders, maternal and foetal inflammatory responses, and maternal and foetal circulatory disorders) and examined mediation of these relationships by SGA. We also assessed exposure-mediator interaction. Models were adjusted for maternal age, race/ethnicity, education, body mass index, parity, and smoking status. RESULTS: All five placental abnormalities were more prevalent in cases than controls. After adjustment for potential confounders, maternal inflammatory response (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.77, 3.75), maternal circulatory disorders OR 4.14, 95% CI 2.93, 5.84, and foetal circulatory disorders OR 4.58, 95% CI 3.11, 6.74 were strongly associated with stillbirth, and the relationships did not appear to be mediated by SGA status. Associations for developmental disorders and foetal inflammatory response diverged for SGA and non-SGA births, and strong associations were only observed when SGA was not present. CONCLUSIONS: Foetal growth did not mediate the relationships between placental abnormalities and stillbirth. The relationships of stillbirth with maternal and foetal circulatory disorders and maternal inflammatory response appear to be independent of poor foetal growth, while developmental disorders and foetal inflammatory response likely interact with foetal growth to affect stillbirth risk.

Interpregnancy interval and risk of stillbirth: a population-based case control study.

PURPOSE: We examined the association between interpregnancy intervals (IPIs) and stillbirth (defined as fetal death ≥20 weeks), as both short and long IPIs have been associated with adverse perinatal outcomes. Prior pregnancy loss is also a known risk factor for stillbirth, and women who suffer a prior loss often have shorter IPIs. For these reasons, we also sought to quantify the proportion of the association between prior pregnancy loss and subsequent stillbirth risk that may be attributed to a short IPI. METHODS: We used data from the Stillbirth Collaborative Research Network, a multisite case-control study conducted in 2006-2008, restricted to singleton pregnancies among multiparous or multigravid women (985 controls and 291 cases). We accounted for complex sample design and nonparticipation with weighted multivariable logistic regression. RESULTS: In the adjusted models, IPIs <6 months, as compared with a reference of 18-23 months, were associated with increased odds of stillbirth (aOR 1.6, 95% CI: 0.8, 3.4). Long IPIs (60-100 months) were also associated with an increased odds of stillbirth (aOR 2.4, 95% CI: 1.2, 4.5). After control for covariates, about one-fifth (21.2%) of the association of prior pregnancy loss (stillbirth, ectopic pregnancy, molar pregnancy, or spontaneous abortion) and stillbirth may be attributable to a short IPI. CONCLUSIONS: Our results suggest that women who experience a prior pregnancy loss may benefit from additional counseling on adequate birth spacing to reduce subsequent stillbirth risk.

Perceptions of parents and religious leaders regarding minimal invasive tissue sampling to identify the cause of death in stillbirths and neonates: results from a qualitative study.

BACKGROUND: Recently, the minimal invasive tissue sampling (MITS) procedure has been developed to support determination of the cause of death as an alternate to conventional autopsy, especially in countries where complete diagnostic autopsy is not routine. To assess the feasibility of implementation of the MITS procedure for a study to determine cause of death in premature births and stillbirths in south Asia, we explored the views and perceptions of parents and religious leaders on the acceptability of MITS. METHODS: A qualitative study was conducted at the National Institute of Child Health (NICH) hospital of Karachi, Pakistan. Focus group discussions (FGDs) were conducted with parents of newborns who visited well-baby clinics of the NICH hospital for post-natal check-ups. Key-informant interviews (KIIs) were conducted with religious leaders. Data were analyzed using NVivo 10 software. RESULTS: A total of 13 interviews (FGDs = 8; KIIs = 5) were conducted. Three overarching themes were identified: (I) acceptability of MITS; (II) concerns affecting the implementation of MITS; and (III) religious and cultural perspectives. Participants' acceptance of MITS was based on personal, religious, cultural and social beliefs. Parents widely recognized the need for this procedure in cases where the couple had experienced multiple stillbirths, neonatal deaths and miscarriages. Counseling of parents was considered vital to address emotional concerns of the parents and the family. Religious leaders indicated acceptability of the MITS procedure from a religious perspective and advised that respect for the deceased and consent of the guardians is mandatory when performing MITS. CONCLUSIONS: This qualitative study provided a unique opportunity to understand the views of parents and religious leaders towards the use of MITS. Generally, MITS appears to be an acceptable method for identifying the cause of death in neonates and stillbirths, provided that the deceased is respected and buried as soon as possible without any delays and parents are counseled appropriately. Findings from this research are essential in approaching families for consent for MITS.

Including ultrasound scans in antenatal care in low-resource settings: Considering the complementarity of obstetric ultrasound screening and maternity waiting homes in strengthening referral systems in low-resource, rural settings.

Recent World Health Organization (WHO) antenatal care recommendations include an ultrasound scan as a part of routine antenatal care. The First Look Study, referenced in the WHO recommendation, subsequently shows that the routine use of ultrasound during antenatal care in rural, low-income settings did not improve maternal, fetal or neonatal mortality, nor did it increase women's use of antenatal care or the rate of hospital births. This article reviews the First Look Study, reconsidering the assumptions upon which it was built in light of these results, a supplemental descriptive study of interviews with patients and sonographers that participated in the First Look study intervention, and a review of the literature. Two themes surface from this review. The first is that focused emphasis on building the pregnancy risk screening skills of rural primary health care personnel may not lead to adaptations in referral hospital processes that could benefit the patient accordingly. The second is that agency to improve the quality of patient reception at referral hospitals may need to be manufactured for obstetric ultrasound screening, or remote pregnancy risk screening more generally, to have the desired impact. Stemming from the literature, this article goes on to examine the potential for complementarity between obstetric ultrasound screening and another approach encouraged by the WHO, the maternity waiting home. Each approach may address existing shortcomings in how the other is currently understood. This paper concludes by proposing a path toward developing and testing such a hybrid approach.

Factors influencing referrals for ultrasound-diagnosed complications during prenatal care in five low and middle income countries.

BACKGROUND: Ultrasound during antenatal care (ANC) is proposed as a strategy for increasing hospital deliveries for complicated pregnancies and improving maternal, fetal, and neonatal outcomes. The First Look study was a cluster-randomized trial conducted in the Democratic Republic of Congo, Guatemala, Kenya, Pakistan and Zambia to evaluate the impact of ANC-ultrasound on these outcomes. An additional survey was conducted to identify factors influencing women with complicated pregnancies to attend referrals for additional care. METHODS: Women who received referral due to ANC ultrasound findings participated in structured interviews to characterize their experiences. Cochran-Mantel-Haenszel statistics were used to examine differences between women who attended the referral and women who did not. Sonographers' exam findings were compared to referred women's recall. RESULTS: Among 700 referred women, 510 (71%) attended the referral. Among referred women, 97% received a referral card to present at the hospital, 91% were told where to go in the hospital, and 64% were told that the hospital was expecting them. The referred women who were told who to see at the hospital (88% vs 66%), where to go (94% vs 82%), or what should happen, were more likely to attend their referral (68% vs 56%). Barriers to attending referrals were cost, transportation, and distance. Barriers after reaching the hospital were substantial. These included not connecting with an appropriate provider, not knowing where to go, and being told to return later. These barriers at the hospital often led to an unsuccessful referral. CONCLUSIONS: Our study found that ultrasound screening at ANC alone does not adequately address barriers to referrals. Better communication between the sonographer and the patient increases the likelihood of a completed referral. These types of communication include describing the ultrasound findings, including the reason for the referral, to the mother and staff; providing a referral card; describing where to go in the hospital; and explaining the procedures at the hospital. Thus, there are three levels of communication that need to be addressed to increase completion of appropriate referrals-communication between the sonographer and the woman, the sonographer and the clinic staff, and the sonographer and the hospital. TRIAL REGISTRATION: NCT01990625 .

Maternal marijuana use, adverse pregnancy outcomes, and neonatal morbidity.

BACKGROUND: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network previously demonstrated an association between stillbirth and maternal marijuana use as defined by the presence of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in the umbilical cord homogenate. However, the relationship between marijuana use and perinatal complications in live births is uncertain. OBJECTIVE: Our aim was to examine if maternal marijuana use is associated with increased odds of adverse pregnancy outcomes and neonatal morbidity among live-born controls in the Stillbirth Collaborative Research Network cohort. STUDY DESIGN: We conducted a secondary analysis of singleton, live-born controls in the Stillbirth Collaborative Research Network data set. Marijuana use was measured by self-report and/or the presence of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in umbilical cord homogenate. Tobacco use was measured by self-report and/or presence of any cotinine in maternal serum. Adverse pregnancy outcome was a composite of small for gestational age, spontaneous preterm birth resulting from preterm labor with or without intact membranes, and hypertensive disorders of pregnancy. Neonatal morbidity included neonatal intensive care unit admission and composite neonatal morbidity (pulmonary morbidity, necrotizing enterocolitis, seizures, retinopathy of prematurity, infection morbidity, anemia requiring blood transfusion, neonatal surgery, hyperbilirubinemia, neurological morbidity, or death prior to hospital discharge). Effect of maternal marijuana use on the probability of an adverse outcome was estimated using weighted methodology to account for oversampling in the original study. 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid cord homogenate analysis was performed in the subset of women for whom biospecimens were available. Comparisons using logistic modeling, χ2, and t tests were weighted to account for oversampling of preterm births and non-Hispanic blacks. Results are reported as weighted percent and unweighted frequencies. RESULTS: Maternal marijuana use was identified in 2.7% (unweighted frequency 48/1610) of live births. Use was self-reported by 1.6% (34/1610) and detected by 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in cord homogenate for 1.9% (17/897), n = 3 overlapping. Rate of tobacco use was 12.9% (217/1610), with 10.7% (167/1607) by self-report and 9.5% (141/1313) by serum cotinine. The composite adverse pregnancy outcome was not significantly increased in women with marijuana use compared to nonusers (31.2% vs 21.2%; P = .14). After adjustment for tobacco, clinical, and socioeconomic factors, marijuana use was not associated with the composite adverse pregnancy outcome (adjusted odds ratio, 1.29; 95% confidence interval, 0.56-2.96). Similarly, among women with umbilical cord homogenate and serum cotinine data (n = 765), marijuana use was not associated with adverse pregnancy outcomes (adjusted odds ratio, 1.02; 95% confidence interval, 0.18-5.66). Neonatal intensive care unit admission rates were not statistically different between groups (16.9% users vs 9.5% nonusers, P = .12). Composite neonatal morbidity or death was more frequent among neonates of mothers with marijuana use compared to nonusers (14.1% vs 4.5%; P = .002). In univariate comparisons, the components of the composite outcome that were more frequent in neonates of marijuana users were infection morbidity (9.8% vs 2.4%; P < .001) and neurologic morbidity (1.4% vs 0.3%; P = .002). After adjustment for tobacco, race, and other illicit drug use, marijuana use was still associated with composite neonatal morbidity or death (adjusted odds ratio, 3.11; 95% confidence interval, 1.40-6.91). CONCLUSION: Maternal marijuana use was not associated with a composite of small for gestational age, spontaneous preterm birth, or hypertensive disorders of pregnancy. However, it was associated with an increased risk of neonatal morbidity.

Research results from a registry supporting efforts to improve maternal and child health in low and middle income countries.

The National Institute of Child Health and Human Development created and continues to support the Global Network for Women's and Children's Health Research, a partnership between research institutions in the US and low-middle income countries. This commentary describes a series of 15 papers emanating from the Global Network's Maternal and Newborn Health Registry. Using data from 2010 to 2013, the series of papers describe nearly 300,000 pregnancies in 7 sites in 6 countries - India (2 sites), Pakistan, Kenya, Zambia, Guatemala and Argentina. These papers cover a wide range of topics including several dealing with efforts made to ensure data quality, and others reporting on specific pregnancy outcomes including maternal mortality, stillbirth and neonatal mortality. Topics ranging from antenatal care, adolescent pregnancy, obstructed labor, factors associated with early initiation of breast feeding and maintenance of exclusive breast feeding and contraceptive usage are presented. In addition, case studies evaluating changes in mortality over time in 3 countries - India, Pakistan and Guatemala - are presented. In order to make progress in improving pregnancy outcomes in low-income countries, data of this quality are needed.

The association of stillbirth with depressive symptoms 6-36 months post-delivery.

BACKGROUND: Stillbirths (≥ 20 weeks' gestation), which account for about 1 in 200 US pregnancies, may grieve parents deeply. Unresolved grief may lead to persistent depression. METHODS: We compared depressive symptoms in 2009 (6-36 months after index delivery) among consenting women in the Stillbirth Collaborative Research Network's population-based case-control study conducted 2006-08 (n = 275 who delivered a stillbirth and n = 522 who delivered a healthy livebirth (excluding livebirths < 37 weeks, infants who had been admitted to a neonatal intensive care unit or who died). Women scoring > 12 on the Edinburgh Depression Scale were classified as currently depressed. Crude (cOR) and adjusted (aOR) odds ratios and 95% confidence intervals [CI] were computed from univariate and multivariable logistic models, with weighting for study design and differential consent. Marginal structural models examined potential selection bias due to low follow-up. RESULTS: Current depression was more likely in women with stillbirth (14.8%) vs. healthy livebirth (8.3%, cOR 1.90 [95% CI 1.20, 3.02]). However, after control for history of depression and factors associated with both depression and stillbirth, the stillbirth association was no longer significant (aOR 1.35 [95% CI 0.79, 2.30]). Conversely, for the 76% of women with no history of depression, a significant association remained after adjustment for confounders (aOR 1.98 [95% CI 1.02, 3.82]). CONCLUSIONS: Improved screening for depression and referral may be needed for women's health care. Research should focus on defining optimal methods for support of women suffering stillbirth so as to lower the risk of subsequent depression.

Screening obstetric ultrasound training for a 5-country cluster randomized controlled trial.

With decreased equipment cost, provision of ultrasound is now feasible in some low resource settings. Screening obstetric ultrasound may identify potential pregnancy complications and, with this knowledge, allow women to plan to deliver at the appropriate level of care. In this article, we describe a 10-day course with quality assurance activities to train ultrasound-naïve, nonphysician healthcare professionals at midlevel health facilities to perform screening obstetric ultrasound. Those trained will participate in a cluster randomized controlled trial to assess the impact of screening obstetric ultrasound on maternal and newborn outcomes.

Association between stillbirth and illicit drug use and smoking during pregnancy.

OBJECTIVE: To compare illicit drug and smoking use in pregnancies with and without stillbirth. METHODS: The Stillbirth Collaborative Research Network conducted a case-control study from March 2006 to September 2008, covering more than 90% of deliveries to residents of five a priori-defined geographically diverse regions. The study attempted to include all stillbirths and representative liveborn controls. Umbilical cord samples from cases and controls were collected and frozen for subsequent batch analysis. Maternal serum was collected at delivery and batch analyzed for cotinine. RESULTS: For 663 stillbirth deliveries, 418 (63%) had cord homogenate and 579 (87%) had maternal cotinine assays performed. For 1,932 live birth deliveries, 1,050 (54%) had cord homogenate toxicology and 1,545 (80%) had maternal cotinine assays performed. A positive cord homogenate test for any illicit drug was associated with stillbirth (odds ratio [OR] 1.94, 95% confidence interval [CI] 1.16-3.27). The most common individual drug was cannabis (OR 2.34 95% CI 1.13-4.81), although the effect was partially confounded by smoking. Both maternal self-reported smoking history and maternal serum cotinine levels were associated in a dose-response relationship with stillbirth. Positive serum cotinine less than 3 ng/mL and no reported history of smoking (proxy for passive smoke exposure) also were associated with stillbirth (OR 2.06, 95% CI 1.24-3.41). CONCLUSION: Cannabis use, smoking, illicit drug use, and apparent exposure to second-hand smoke, separately or in combination, during pregnancy were associated with an increased risk of stillbirth. Because cannabis use may be increasing with increased legalization, the relevance of these findings may increase as well. LEVEL OF EVIDENCE: II.

Effect of corticosteroid interval on markers of inflammation in spontaneous preterm birth.

OBJECTIVE: The objective of the study was to evaluate whether the time interval from corticosteroid administration to delivery is associated with variations in inflammatory/infectious markers in women with spontaneous preterm birth (SPTB). STUDY DESIGN: We conducted a secondary analysis of a prospectively collected cohort of women experiencing SPTB from 23(0/7) to 31(6/7) weeks. Patients were categorized by corticosteroid receipt and time interval until delivery. Prevalence of markers of inflammation and colonization/infection (cord blood interleukin [IL]-6 levels; Ureaplasma urealyticum [UU], Mycoplasma hominis [MH], and other anaerobic/aerobic cultures; histology of the placental disc, membranes and cord) were compared between groups using χ(2) and Mantel-Haenszel tests. RESULTS: Two hundred seventy-three patients had SPTB. Prevalence of elevated IL-6 (P = .028) and positive UU/MH cultures (P = .019) were highest in women not receiving corticosteroids and those delivering more than 7 days from receipt. The prevalence of both decreased in groups with delivery delayed at least 12 hours but increased as the interval lengthened to more than 48 hours. Overall positive placental cultures also nadired among those delivering at 12-24 hours after corticosteroids (P = .049). As the interval increased, prevalence of acute inflammation at the rupture site increased (P = .017). There were similar, but nonsignificant, increases in chorionic plate inflammation and funisitis. CONCLUSION: The relationship between time interval from corticosteroids and evidence of inflammation in women experiencing SPTB is U shaped, suggesting earlier stages of inflammation in women with delayed delivery or transient decreases of inflammation in response to corticosteroids. This warrants further investigation to elucidate the natural history of SPTB and its modulation by corticosteroids.

Stillbirth: knowledge and practice among U.S. obstetrician-gynecologists.

OBJECTIVE: To determine knowledge of U.S. obstetrician-gynecologists (OBGYNs) and individual and institutional practices regarding stillbirth. STUDY DESIGN: We surveyed 1,000 members of the American College of Obstetricians and Gynecologists regarding their knowledge of risk factors and causes of stillbirth and self-rated performance in stillbirth management. RESULTS: Of the 499 who responded, 365 currently practiced obstetrics. Knowledge regarding epidemiology, risk factors, and effective interventions to reduce stillbirth was only fair. About 30% of respondents were unaware that preeclampsia, advanced maternal age, elevated α-fetoprotein, multiple gestation, cigarette smoking, illicit drug use, and being postterm increased risk. Tests to identify stillbirth causes were not performed consistently. Forty-two percent of respondents did not review test results to determine cause. Most hospitals did not have protocols for stillbirth evaluation nor preprinted forms to obtain appropriate stillbirth tests. Stillbirth audits with feedback were rarely performed. CONCLUSIONS: OBGYN knowledge and institutional practice regarding stillbirth could be substantially improved. Residency programs need improved education regarding stillbirth. Hospitals and their OBGYN departments should focus more on stillbirth through continuing education programs and grand rounds and develop stillbirth management protocols and standardized order sheets to appropriately evaluate stillbirths. Audits that evaluate cause of death and preventability with a feedback loop focused on improvement in care should be considered.

Maternal and Early Childhood Risk Factors for Overweight and Obesity among Low-Income Predominantly Black Children at Age Five Years: A Prospective Cohort Study.

Objective. To identify maternal and early childhood risk factors for obesity and overweight among children at age 5 in the state of Alabama. Methods. We recruited 740 mothers during early pregnancy from University of Alabama Prenatal Clinics in a prospective cohort study and followed them throughout pregnancy. We followed their children from birth until 5 years of age. The main outcome measure was obesity (BMI for age and sex ≥ 95th percentile) at 5 years of age. We used poisson regression with robust variance estimation to compute risk ratio (RR). Results. At the 5th year of followup, 71 (9.6%) of the children were obese and 85 (11.5%) were overweight (BMI ≥ 85th-<95th percentile). In multivariable analysis, maternal prepregnancy overweight (RR: 2.30, 95% CI: 1.29-4.11) and obesity (RR: 2.53, 95% CI: 1.49-4.31), and child's birth weight >85th percentile (RR: 2.04, 95% CI: 1.13-3.68) were associated with childhood obesity. Maternal prepregnancy BMI, birth weight, and maternal smoking were associated with the child being overweight 1-12 cigarettes/day versus 0 cigarettes/day (RR: 1.40, 95% CI: 1.02-1.91). Conclusion. Children of overweight and obese mothers, and children with higher birth weight, are more likely to be obese and overweight at age 5. Maternal smoking 1-12 cigarettes per day is associated with the child being overweight.

The antibiotic treatment of PPROM study: systemic maternal and fetal markers and perinatal outcomes.

OBJECTIVE: We sought to correlate maternal and cord blood cytokine and intercellular adhesion molecule-1 levels with antibiotic exposure and perinatal outcomes after conservatively managed preterm premature rupture of the membranes. STUDY DESIGN: Conservatively managed women with preterm premature rupture of the membranes at 24-32 weeks had blood sampling at randomization (n = 222) and delivery (n = 121). Plasma from these, and umbilical cord blood (n = 196), was stored at -70°C. Interleukin (IL)-6, IL-10, granulocyte colony-stimulating factor (G-CSF), tumor necrosis factor-α, and intercellular adhesion molecule-1 levels were assessed for associations with antibiotic treatment, latency, amnionitis, neonatal sepsis, pneumonia, and composite neonatal morbidity. RESULTS: Cord blood IL-6 and G-CSF were higher than maternal levels. Antibiotic treatment lowered only maternal G-CSF (P = .01). Elevated maternal cytokine levels were associated with delivery within 7 days and with development of chorioamnionitis. All umbilical cord blood markers were increased with amnionitis (P ≤ .01 for each). No maternal marker was associated with neonatal morbidities. Cord G-CSF and IL-6 were increased with neonatal sepsis within 72 hours of birth (P = .004 for both), and with composite neonatal morbidity (P = .001 and .002, respectively). Maternal and umbilical cord cytokine levels demonstrated low predictive values for perinatal outcomes. CONCLUSION: Umbilical cord blood cytokine values are higher than maternal levels, suggesting significant fetal/placental contribution. Maternal and umbilical cord cytokine levels are not adequately predictive to be used clinically.