Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial.

BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point. RESULTS: At 12-wk gestation and 3-mo postpartum, no statistical differences in mean SZC were observed among arms. At 34-wk, mean SZC for arms 1 and 2 were significantly higher than for arm 3 (50.3, 50.8, 47.8 µg/dL, respectively; P = 0.005). Results were not impacted by correction for inflammation or albumin concentrations. Prevalence of hypozincemia at 12-wk (<56 µg/dL) was 23% in Guatemala, 26% in India, and 65% in Pakistan; at 34 wk (<50 µg/dL), 36% in Guatemala, 48% in India, and 74% in Pakistan; and at 3-mo postpartum (<66 µg/dL) 79% in Guatemala, 91% in India, and 92% in Pakistan. Maternal hypozincemia at 34-wk was associated with lower birth length-for-age Z-scores (all sites P = 0.013, Pakistan P = 0.008) and weight-for-age Z-scores (all sites P = 0.017, Pakistan P = 0.022). CONCLUSIONS: Despite daily zinc supplementation for ≥7 mo, high rates of maternal hypozincemia were observed. The association of hypozincemia with impaired fetal growth suggests widespread zinc deficiency in these settings. This trial is registered at clinicaltrials.gov as #NCT01883193.

Infant and young child feeding indicators are positively associated with length and family care indicators in the children of the Women First trial participants.

This research describes the proportion of children in four low- and middle-income countries with adequate dietary practices at 6, 12, 18 and 24 months of age and how these practices changed over time using the World Health Organisation and UNICEF's infant young child feeding (IYCF) indicators. The associations between the IYCF indicators and anthropometric z-scores from 6 to 24 months, and between the IYCF indicators and the family care indicators (FCIs) at 24 months are described. This was a longitudinal study of offspring from participants in the Women First Preconception Maternal Nutrition Trial conducted in Sud-Ubangi, Democratic Republic of Congo; Chimaltenango, Guatemala; Belagavi, North Karnataka, India; and Thatta, Sindh Province, Pakistan. The frequency of the minimum dietary diversity (MDD), minimum meal frequency (MMF), and minimum adequate diet (MAD) increased between 6 and 24 months, but even at 24 months MAD remained below 50% at all sites. MDD (ß = 0.12; 95% CI = 0.04-0.22) and MMF (ß = 0.10; 95% CI = 0.03-0.17) were positively associated with length-for-age z-score at 24 months. All IYCF indicators were positively associated with mean total FCI score: MDD (proportion ratio [PR] = 1.04; 95% CI = 1.02-1.07), MMF (PR = 1.02; 95% CI = 1.01-1.04), MAD (PR = 1.05; 95% CI = 1.02-1.08). Although there are multiple barriers to young children having an adequate diet, our results support a positive association between familial interactions and improved IYCF feeding practices.

Associations between ambient temperature and pregnancy outcomes from three south Asian sites of the Global Network Maternal Newborn Health Registry: A retrospective cohort study.

OBJECTIVE: Growing evidence suggests that environmental heat stress negatively influences fetal growth and pregnancy outcomes. However, few studies have examined the impact of heat stress on pregnancy outcomes in low-resource settings. We combined data from a large multi-country maternal-child health registry and meteorological data to assess the impacts of heat stress. DESIGN: Retrospective cohort study. SETTING: Three sites based in south Asia as part of the Global Network for Women's and Children's Health research in India (Belagavi and Nagpur) and Pakistan (Thatta). POPULATION OR SAMPLE: Data from women enrolled between 2014 and 2020 in the Global Network's Maternal Newborn Health Registry (MNHR), a prospective, population-based registry of pregnancies, were used. METHODS: A total of 126 273 pregnant women were included in this analysis. Daily maximal air temperatures (Tmax ) were acquired from local meteorological records. Associations between averages of daily maximal temperatures for each trimester and main outcomes were analysed using a modified Poisson regression approach. MAIN OUTCOMES MEASURES: Incidence of stillbirth, preterm birth, low birthweight (<2500 g) or evidence of pregnancy hypertension or pre-eclampsia. RESULTS: In the overall cohort, risk of preterm birth was positively associated with greater temperature in the second trimester (relative risk [RR] 1.05, 95% CI 1.02-1.07, p = 0.0002). Among individual sites, the risk of preterm birth was greatest in Nagpur (RR 1.07, 95% CI 1.03-1.11, p = 0.0005) and associated with second-trimester temperature. The overall risk of low birthweight was associated with ambient temperature in second trimester (RR 1.02, 95% CI 1.01-1.04, p = 0.01). The risk for LBW was associated with first-trimester heat in Thatta and with second-trimester heat in Nagpur. Finally, the overall risk of gestational hypertensive disease was associated with greater temperature in the third trimester among all sites (RR 1.07, 95% CI 1.02-1.12, p = 0.005) and was particularly significant for Nagpur (RR 1.13, 95% CI 1.05-1.23, p = 0.002). These findings highlight the increased risk of detrimental obstetric and neonatal outcomes with greater temperature. CONCLUSION: In a multi-country, community-based study, greater risk of adverse outcomes was observed with increasing temperature. The study highlights the need for deeper understanding of covarying factors and intervention strategies, especially in regions where high temperatures are common.

Role of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis.

BACKGROUND: Iron deficiency anemia is a common public health issue among women of reproductive age (WRA) because it can result in adverse maternal and birth outcomes. Although studies are undertaken to assess iron efficacy, some gaps and limitations in the existing literature need to be addressed. To fill the gaps, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the role of iron in reducing anemia among WRA in low-middle-income countries (LMICs). METHODS: A comprehensive search strategy was used to search Medline through PubMed, Embase, and Science Direct for RCTs published between 2000 and 2020. The primary outcome was the mean change in hemoglobin level. We used standardized mean differences and their respective 95% CI to estimate the pooled effect. We used I2 statistics and Egger's test to assess heterogeneity and publication bias, respectively. This review was carried out in accordance with revised guidelines based on the Preferred Reporting Items for Systematic Review and Meta-analysis. RESULTS: The findings showed that iron therapy improved hemoglobin and ferritin levels, though the results varied across studies. An overall pooled effect estimate for the role of iron therapy in improving the hemoglobin levels among WRA was -0.71 (95% CI: -1.27 to -0.14) (p = 0.008). Likewise, the overall pooled effect estimate for the role of iron therapy in improving the ferritin levels among WRA was -0.76 (95% CI: -1.56 to 0.04) (p = 0.04). The heterogeneity (I2) across included studies was found to be statistically significant for studies assessing hemoglobin (Q = 746.93, I2 = 97.59%, p = 0.000) and ferritin level (Q = 659.95, I2 = 97.88%, p = 0.000). CONCLUSION: Iron therapy in any form may reduce anemia's burden and improve hemoglobin and ferritin levels, indicating improvement in iron-deficiency anemia. More evidence is required, however, to assess the morbidity associated with iron consumption, such as side effects, work performance, economic outcomes, mental health, and adherence to the intervention, with a particular focus on married but non-pregnant women planning a pregnancy in the near future. TRIAL REGISTRATION: Registered with PROSPERO and ID is CRD42020185033.

Quality of care assessment for small and sick newborns and young infants in Pakistan: findings from a cross-sectional study.

INTRODUCTION: Pakistan is facing a challenging situation in terms of high newborn mortality rate. Securing pregnancy and delivery care may not bring a substantial reduction in neonatal mortality, unless coupled with the provision of quality inpatient care for small and sick newborns and young infants (NYIs). We undertook this study to assess the availability and quality of newborn care services provided and the readiness of inpatient care for NYIs in Pakistan. METHODS: We conducted a cross-sectional study across Pakistan from February to June 2019, using a purposive sample of 61% (23) of the 38 sick newborn care units at public sector health care facilities providing inpatient care for small and sick NYIs. We interviewed facility managers and health care providers by using structured questionnaires. We observed facility infrastructure and relevant metrics related to the quality of inpatient care such as types of infant care units and essential equipment, drugs, staffing cadre and facility management practices, quality assurance activities, essential services for small and sick NYI care, discharge planning, and support, quality of NYIs care record, and health information system. RESULTS: Of the 23 facilities assessed, 83% had newborn intensive care units (NICUs), 74% reported Special Care Units (SCUs), and only 44% had Kangaroo Mother Care (KMC) Units. All facilities had at least one paediatrician, 13% had neonatologists and neonatal surgeons each. Around 61 and 13% of the facilities had staff trained in neonatal resuscitation and parental counseling, respectively. About 35% of the facilities monitored nosocomial infection rates, with management and interdisciplinary team meetings reported from 17 and 30% of the facilities respectively preceding the survey. Basic interventions for NYIs were available in 43% of the facilities, only 35% of facilities had system in place to monitor nosocomial infections for NYI care. Most (73%) of reviewed records of NYIs at 1-2 days had information on the birth weight, temperature recording (52%), while only a quarter (25%) of the observed records documented danger signs. Mechanism to support discharge care by having linkages with community workers was present in 13% of the facilities, while only 35% of the facilities have strategies to promote adherence after discharge. Majority (78%) of facilities reported monitoring any newborn/ neonatal care indicators, while none of the sub-units within facilities had consolidated information on stillbirths and neonatal deaths. CONCLUSION: The study has demonstrated important gaps in the quality of small and sick NYI inpatient care in the country. To avert neonatal mortality in the country, provincial and district governments have to take actions in improving the quality of inpatient care.

Growth from Birth Through Six Months for Infants of Mothers in the "Women First" Preconception Maternal Nutrition Trial.

OBJECTIVE: To evaluate whether the fetal linear growth effects of maternal nutrition supplementation would be maintained through 6 months postnatal age. STUDY DESIGN: The Women First trial was a multicountry, individually randomized clinical trial that compared the impact of maternal nutrition supplementation initiated preconception (Arm 1) vs at ∼11 weeks of gestation (Arm 2), vs no supplement (Arm 3); the intervention was discontinued at delivery. Trial sites were in Democratic Republic of Congo, Guatemala, India, and Pakistan. Analysis includes 2421 infants born to 2408 randomized women. Primary outcome was the trajectory of length-for-age z scores (LAZ) by arm, based on assessments at birth and 1, 3, and 6 months. We fitted longitudinal models on growth from birth to 6 months using generalized estimating equations; maternal intervention effects were evaluated, adjusting for site and baseline maternal covariates. RESULTS: Linear growth for Arms 1 and 2 was statistically greater than for Arm 3 in 3 of the 4 countries, with average pairwise mean differences in LAZ of 0.25 (95% CI 0.15-0.35; P < .001) and 0.19 (95% CI 0.09-0.28; P < .001), respectively. Compared with Arm 3, average overall adjusted relative risks (95% CI) for stunting (LAZ <-2) were lower for Arms 1 and 2: 0.76 (0.66-0.87; P < .001) and 0.77 (0.67-0.88; P < .001), respectively. CONCLUSIONS: Improved linear growth in early infancy observed for the 2 intervention arms supports the critical importance of maternal nutrition before conception and in the early phase of gestation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01883193.

Preconceptional Lipid-Based Nutrient Supplementation in 2 Low-Resource Countries Results in Distinctly Different IGF-1/mTOR Placental Responses.

BACKGROUND: Preconceptional maternal small-quantity lipid-based nutrient supplementation (SQLNS) improved intrauterine linear growth in low-resource countries as demonstrated by the Women First Preconception Maternal Nutrition Trial (WF). Fetal growth is dependent on nutrient availability and regulated by insulin-like growth factor 1 (IGF-1) through changes in placental transfer capacity, mediated by the mechanistic target of rapamycin (mTOR) pathway. OBJECTIVES: Our objective was to evaluate the role of placental mTOR and IGF-1 signaling on fetal growth in women from 2 low-resource countries with high rates of stunting after they received preconceptional SQLNS. METHODS: We studied 48 women from preconception through delivery who were from Guatemala and Pakistan and received SQLNS or not, as part of the WF study. Placental samples were obtained at delivery (control, n = 24; SQLNS, n = 24). Placental protein or mRNA expression of eukaryotic translation initiation factor binding protein-1 (4E-BP1), ribosomal protein S6 (rpS6), AMP-activated protein kinase α (AMPKA), IGF-1, insulin-like growth factor receptor (IGF-1R), and pregnancy associated plasma protein (PAPP)-A, and DNA methylation of the IGF1 promoter were determined. Maternal serum IGF-1, insulin-like growth factor binding protein (IGFBP)-3, IGFBP-4, IGFBP-5, PAPP-A, PAPP-A2, and zinc were measured. RESULTS: Mean ± SEM maternal prepregnancy BMI differed between participants in Guatemala (26.5 ± 1.3) and Pakistan (19.8 ± 0.7) (P < 0.001). In Pakistani participants, SQLNS increased the placental rpS6(T37/46):rpS6 ratio (1.5-fold) and decreased the AMPKA(T172):AMPKA ratio. Placental IGF1 mRNA expression was positively correlated with birth length and birth weight z-scores. Placental PAPP-A (30-fold) and maternal serum zinc (1.2-fold) increased with SQLNS. In Guatemalan participants SQLNS did not influence placental mTOR signaling. Placental IGF-1R protein expression was positively associated with birth length and birth weight z-scores. SQLNS increased placental PAPP-A (40-fold) and maternal serum IGFBP-4 (1.6-fold). CONCLUSIONS: In Pakistani pregnant women with poor nutritional status, preconceptional SQLNS activated placental mTOR and IGF-1 signaling and was associated with improved fetal growth. In contrast, in Guatemalan women SQLNS did not activate placental nutrient-sensing pathways. In populations experiencing childhood stunting, preconceptional SQLNS improves placental function and fetal growth only in the context of poor maternal nutrition. This trial was registered at clinicaltrials.gov as NCT01883193.

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.

Predictors of iron consumption for at least 90 days during pregnancy: Findings from National Demographic Health Survey, Pakistan (2017-2018).

BACKGROUND: Iron supplementation is considered an imperative strategy for anemia prevention and control during pregnancy in Pakistan. Although there is some evidence on the predictors of iron deficiency anemia among Pakistani women, there is a very limited understanding of factors associated with iron consumption among Pakistani pregnant women. Thus, this study aimed to investigate the predictors of iron consumption for at least ≥90 days during pregnancy in Pakistan. METHODS: We analyzed dataset from the nationally representative Pakistan Demographic Health Survey 2017-2018. The primary outcome of the current study was the consumption of iron supplementation for ≥90 days during the pregnancy of the last birth. Women who had last childbirth 5 years before the survey and who responded to the question of iron intake were included in the final analysis (n = 6370). We analyzed the data that accounted for complex sampling design by including clusters, strata, and sampling weights. RESULTS: Around 30% of the women reported consumed iron tablets for ≥90 days during their last pregnancy. In the multivariable logistic regression analysis, we found that factors such as women's age (≥ 25 years) (adjusted prevalence ratio (aPR) = 1.52; 95% CI: 1.42-1.62)], wealth index (rich/richest) (aPR = 1.25; [95% CI: 1.18-1.33]), primary education (aPR = 1.33; [95% CI: 1.24-1.43), secondary education (aPR = 1.34; [95% CI: 1.26-1.43), higher education (aPR = 2.13; [95% CI: 1.97-2.30), women's say in choosing husband (aPR = 1.68; [95% CI: 1.57-1.80]), ≥ five antenatal care visits (aPR =2.65; [95% CI (2.43-2.89]), history of the last Caesarian-section (aPR = 1.29; [95% CI: 1.23-1.36]) were significantly associated with iron consumption for ≥90 days. CONCLUSION: These findings demonstrate complex predictors of iron consumption during pregnancy in Pakistan. There is a need to increase the number of ANC visits and the government should take necessary steps to improve access to iron supplements by targeting disadvantaged and vulnerable women who are younger, less educated, poor, and living in rural areas.

Quality of inpatient care of small and sick newborns in Pakistan: perceptions of key stakeholders.

BACKGROUND: In LMICs including Pakistan, neonatal health and survival is a critical challenge, and therefore improving the quality of facility-based newborn care services is instrumental in averting newborn mortality. This paper presents the perceptions of the key stakeholders in the public sector to explore factors influencing the care of small and sick newborns and young infants in inpatient care settings across Pakistan. METHODS: This exploratory study was part of a larger study assessing the situation of newborn and young infant in-patient care provided across all four provinces and administrative regions of Pakistan. We conducted 43 interviews. Thirty interviews were conducted with the public sector health care providers involved in newborn and young infant care and 13 interviews were carried out with health planners and managers working at the provincial level. A semi-structured interview guide was used to explore participants' perspectives on enablers and barriers to the quality of care provided to small and sick newborns at the facility level. The interviews were manually analyzed using thematic content analysis. FINDINGS: The study respondents identified multiple barriers contributing to the poor quality of small and sick newborn care at inpatient care settings. This includes an absence of neonatal care standards, inadequate infrastructure and equipment for the care of small and sick newborns, deficient workforce for neonatal case management, inadequate thermal care management for newborns, inadequate referral system, absence of multidisciplinary approach in neonatal case management and need to institute strong monitoring system to prevent neonatal deaths and stillbirths. The only potential enabling factor was the improved federal and provincial oversight for reproductive, maternal, and newborn care. CONCLUSION: This qualitative study was insightful in identifying the challenges that influence the quality of inpatient care for small and sick newborns and the resources needed to fix these. There is a need to equip Sick Newborn Care Units with needed supplies, equipment and medicines, deployment of specialist staff, strengthening of in-service training and staff supervision, liaison with the neonatal experts in customizing neonatal care guidelines for inpatient care settings and to inculcate the culture for inter-disciplinary team meetings at inpatient care settings across the country.

Improved first trimester maternal iodine status with preconception supplementation: The Women First Trial.

Maternal iodine (I) status is critical in embryonic and foetal development. We examined the effect of preconception iodine supplementation on maternal iodine status and on birth outcomes. Non-pregnant women in Guatemala, India and Pakistan (n ~ 100 per arm per site) were randomized ≥ 3 months prior to conception to one of three intervention arms: a multimicronutrient-fortified lipid-based nutrient supplement containing 250-µg I per day started immediately after randomization (Arm 1), the same supplement started at ~12 weeks gestation (Arm 2) and no intervention supplement (Arm 3). Urinary I (µg/L) to creatinine (mg/dl) ratios (I/Cr) were determined at 12 weeks for Arm 1 versus Arm 2 (before supplement started) and 34 weeks for all arms. Generalized linear models were used to assess the relationship of I/Cr with arm and with newborn anthropometry. At 12 weeks gestation, adjusted mean I/Cr (µg/g) for all sites combined was significantly higher for Arm 1 versus Arm 2: (203 [95% CI: 189, 217] vs. 163 [95% CI: 152, 175], p < 0.0001). Overall adjusted prevalence of I/Cr < 150 µg/g was also lower in Arm 1 versus Arm 2: 32% (95% CI: 26%, 38%) versus 43% (95% CI: 37%, 49%) (p = 0.0052). At 34 weeks, adjusted mean I/Cr for Arm 1 (235, 95% CI: 220, 252) and Arm 2 (254, 95% CI: 238, 272) did not differ significantly but were significantly higher than Arm 3 (200, 95% CI: 184, 218) (p < 0.0001). Nominally significant positive associations were observed between I/Cr at 12 weeks and birth length and head circumference z-scores (p = 0.028 and p = 0.005, respectively). These findings support the importance of first trimester iodine status and suggest need for preconception supplementation beyond salt iodization alone.

Desire to limiting child birth and the associated determinants among married females: Sukh Survey-Karachi, Pakistan.

OBJECTIVE: High rates of population growth negatively influence the social and economic development of a country. This study aimed to determine the women's desire to limiting child birth in future (fertility intention) and its determinants among Pakistani women of reproductive age resident of Karachi. METHODS: A community-based, multistage cross-sectional study was carried out among residents of the squatter settlements in Karachi. The were 4,485 married residents, and currently non-pregnant females of 18 to 49 years old. Framework adapted has been based on "Pullum 1980" to operationalize the outcome of determining the desire to limiting childbearing and the factors related with controlling the family size. Multivariable logistic regression using SPSS 13.0 was used. RESULTS: The survey comprised of a total sample of 4485 females who participated and acquiring a median (interquartile range) age of 30 (25 to 35) years. Whereas, the living children count was found to be [median: 3 children; (IQR: 2 to 4)]. From the total, 2109 (47%) wanted to limit the future child birth. Multivariable logistic analysis showed that women who did not want to limit child birth significantly (p-value <0.05) belonged to age groups 18 to 27 years (adjusted odds ratio [aOR]=0.25), and 28 - 37 years (aOR=0.39) compared to the women aged > 37 years (referent category), who belonged to poor wealth category (aOR=0.41), were ever contraceptive users (aOR=0.49), were currently not a contraceptive user (aOR=0.53), not educated (aOR=0.34), and having sons less than the daughters (aOR=0.74). Conversely, females with perceived family structure of ≤two children ideally (aOR=2.62), were autonomous (aOR=1.25) and who had equal daughters and sons (aOR=1.13) rather than more number of sons, had more probability to limiting child birth at a statistically significance (p-value) of less than 0.05. CONCLUSIONS: The survey highlights the strategic independent determinants and there is a need of devising behaviour modification modalities accordingly to expedite the use of contraceptive methods and to encourage fertility decline among women.

Factors affecting the utilization of antenatal care among married women of reproductive age in the rural Thatta, Pakistan: findings from a community-based case-control study.

BACKGROUND: There are differences in antenatal care (ANC) utilization between urban and rural areas of Pakistan. Although multiple factors have been studied affecting the utilization of general health care services, the effect of road network distance particularly on the utilization of ANC has not been assessed. Therefore, this study aimed to determine the association between road network distance from a health care facility and utilization of the ANC among women of reproductive age in Thatta Pakistan. METHODS: A community-based case-control study was conducted in district Thatta, Pakistan. Women who did not utilize ANC services during their last pregnancy were considered as cases, while controls were the women who utilized ANC services during their last pregnancy. Questions related to socio-demographic, access-related factors and utilization of ANC were asked from women. Road network distance was calculated from the women's home to the health care facility providing ANC services. Logistic regression analysis was performed. RESULTS: A total of 380 participants were interviewed in this study. Participants' mean age and parity were 28 years (SD 5.65), and 3.5 (SD 2.6) respectively. The multivariate analysis showed that women living at a shorter distance of less than 5 km were 1.21 times likely to utilize ANC services [Adjusted OR. 1.21; 95% CI (0.49-2.99)]. Moreover, nulliparous women were 4.10 times likely to utilize antenatal care [Adjusted OR. 4.10; 95% CI (1.10-15.26)]. Similarly, women who had knowledge of antennal care were 6.60 times likely to utilize ANC services [Adjusted OR. 6.60; 95% CI (3.33-13.05)]. Women having electricity in their households were 3.15 times likely to utilize the ANC services [Adjusted OR. 3.11 95% CI (1.51-6.41)]. Women, living in well-constructed (Pakka) houses were 2.58 times likely to utilize the ANC services [Adjusted O.R: 2.58; 95% CI (1.15-5.82)]. CONCLUSION: Road network distance has no measurable impact on ANC utilization among married women in Thatta district, Pakistan. Nulliparous women having knowledge of ANC living in well-constructed houses equipped with electricity were found to be utilizers of ANC services. It is recommended that awareness and health education sessions should be arranged for pregnant women in rural Pakistan.

Hemoglobin concentrations and adverse birth outcomes in South Asian pregnant women: findings from a prospective Maternal and Neonatal Health Registry.

BACKGROUND: While the relationship between hemoglobin (Hb) concentrations and pregnancy outcomes has been studied often, most reports have focused on a specific Hb cutoff used to define anemia. Fewer studies have evaluated pregnancy outcomes across the entire range of Hb values. Moreover, to date, most studies of the relationship of Hb concentrations to pregnancy outcomes have been done in high-income countries. Thus, we have sought to determine the relationship between the range of maternal Hb concentrations and adverse birth outcomes among South Asian pregnant women. METHODS: For this study, we used data collected from two South Asian countries (Pakistan - Sindh Province and two sites in India - Belagavi and Nagpur) in a prospective maternal and newborn health registry study. To assess the association between Hb concentrations and various maternal and fetal outcomes, we classified the Hb concentrations into seven categories. Regression analyses adjusting for multiple potential confounders were performed to assess adverse pregnancy outcomes across the range of Hb concentrations. FINDINGS: Between January 2012 and December 2018, 130,888 pregnant women were enrolled in the South Asian sites had a Hb measurement available, delivered and were included in the analyses. Overall, the mean Hb concentration of pregnant women from the sites was 9.9 g/dL, 10.0 g/dL in the Indian sites and 9.5 g/dL in the Pakistan site. Hb concentrations < 7 g/dL were observed in 6.9% of the pregnant Pakistani women and 0.2% of the Indian women. In both the Pakistani and Indian sites, women with higher parity and women with no formal education had lower Hb concentrations. In the Pakistani site, women > 35 years of age, women with ≥4 children and those who enrolled in the third trimester were more likely to have Hb concentrations of < 7 g/dL but these associations were not found for the Indian sites. When adjusting for potential confounders, for both India and Pakistan, lower Hb concentrations were associated with stillbirth, preterm birth, lower mean birthweight, and increased risk of low birthweight. In the Pakistani site, there was evidence of a U-shaped relationship between Hb concentrations and low birth weight, and neonatal mortality, and in India with hypertensive disease. INTERPRETATION: This study documented the relationship between maternal Hb concentrations and adverse pregnancy outcomes in women from the Pakistani and Indian sites across the range of Hb values. Both low and high Hb concentrations were associated with risk of at least some adverse outcomes. Hence, both low and high values of Hb should be considered risk factors for the mother and fetus.

Factors associated with anemia among women of the reproductive age group in Thatta district: study protocol.

BACKGROUND: Maternal anemia is a leading public health issue placing pregnant women at higher risk of low birth weight, preterm birth, perinatal mortality, and neonatal mortality. Women in developing countries are at higher risk of anemia which could be either due to micronutrient deficiencies, hemoglobinopathies, infections or other socio-demographic factors. Thus, it is highly essential to explore the factors of anemia among women of the reproductive age group in order to design suitable interventions. The primary objective of this study is to assess the biological and socio-demographic factors that are associated with anemia among the women of the reproductive age group in Thatta district. METHODS: An exploratory mixed method study using quantitative and qualitative approaches will be conducted in district Thatta Pakistan from September 2018 to January 2019. In the qualitative phase, data will be collected through focus group discussions and key informant interviews to understand the perceptions of women, their husbands and healthcare providers about anemia. In addition, a quantitative approach using cross-sectional study will be conducted to determine biological and socio-demographic factors associated with anemia. Approximately 150 non-pregnant women and their spouses will be included in the quantitative component of the study. In addition to thematic analysis for the qualitative component, Logistic regression will be done to calculate adjusted Odds ratios with their respective 95% CIs to assess the factors associated with anemia. DISCUSSION: The better understanding of biological, socio-demographic factors and community perceptions of anemia will help us to design strategies and interventions to better address anemia during the reproductive cycle in rural areas of Pakistan. This will help the researchers and policymakers to take the appropriate action accordingly by designing suitable approaches to address the specific type of anemia in the rural population of Pakistan. This will, in turn, reduce the chances of adverse maternal and fetal outcomes associated with anemia.

A Prospective, Population-Based Study of Trends in Operative Vaginal Delivery Compared to Cesarean Delivery Rates in Low- and Middle-Income Countries, 2010-2016.

OBJECTIVE: Few data are available on cesarean delivery and operative vaginal delivery trends in low- and middle-income countries. Our objective was to analyze a prospective population-based registry including eight sites in seven low- and middle-income countries to observe trends in operative vaginal delivery versus cesarean delivery rates over time, across sites. STUDY DESIGN: A prospective population-based study, including home and facility births among women enrolled from 2010 to 2016, was performed in communities in Argentina, Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, and Zambia. Women were enrolled during pregnancy and delivery outcome data were collected. RESULTS: We analyzed 354,287 women; 4,119 (1.2%) underwent an operative vaginal delivery and 45,032 (11.2%) delivered by cesarean. Across all sites with data for 7 years, rates of operative vaginal delivery decreased from 1.6 to 0.3%, while cesarean delivery increased from 6.4 to 14.4%. Similar trends were seen when individual country data were analyzed. Operative vaginal delivery rates decreased in both hospitals and clinics, except in the hospital setting at one of the Indian sites. CONCLUSION: In low- and middle-income countries, operative vaginal delivery is becoming less utilized while cesarean delivery is becoming an increasingly common mode of delivery.

IVC filter placements in children: nationwide comparison of practice patterns at adult and children's hospitals using the Kids' Inpatient Database.

BACKGROUND: Inferior vena cava (IVC) filter placement in children has been described in literature, but there is variability with regard to their indications. No nationally representative study has been done to compare practice patterns of filter placements at adult and children's hospitals. OBJECTIVE: To perform a nationally representative comparison of IVC filter placement practices in children at adult and children's hospitals. MATERIALS AND METHODS: The 2012 Kids' Inpatient Database was searched for IVC filter placements in children <18 years of age. Using the International Classification of Diseases, 9th Revision (ICD-9) code for filter insertion (38.7), IVC filter placements were identified. A small number of children with congenital cardiovascular anomalies codes were excluded to improve specificity of the code used to identify filter placement. Filter placements were further classified by patient demographics, hospital type (children's and adult), United States geographic region, urban/rural location, and teaching status. Statistical significance of differences between children's or adult hospitals was determined using the Wilcoxon rank sum test. RESULTS: A total of 618 IVC filter placements were identified in children <18 years (367 males, 251 females, age range: 5-18 years) during 2012. The majority of placements occurred in adult hospitals (573/618, 92.7%). Significantly more filters were placed in the setting of venous thromboembolism in children's hospitals (40/44, 90%) compared to adult hospitals (246/573, 43%) (P<0.001). Prophylactic filters comprised 327/573 (57%) at adult hospitals, with trauma being the most common indication (301/327, 92%). The mean length of stay for patients receiving filters was 24.5 days in children's hospitals and 18.4 days in adult hospitals. CONCLUSION: The majority of IVC filters in children are placed in adult hospital settings. Children's hospitals are more likely to place therapeutic filters for venous thromboembolism, compared to adult hospitals where the prophylactic setting of trauma predominates.

Trends and determinants of stillbirth in developing countries: results from the Global Network's Population-Based Birth Registry.

BACKGROUND: Stillbirth rates remain high, especially in low and middle-income countries, where rates are 25 per 1000, ten-fold higher than in high-income countries. The United Nations' Every Newborn Action Plan has set a goal of 12 stillbirths per 1000 births by 2030 for all countries. METHODS: From a population-based pregnancy outcome registry, including data from 2010 to 2016 from two sites each in Africa (Zambia and Kenya) and India (Nagpur and Belagavi), as well as sites in Pakistan and Guatemala, we evaluated the stillbirth rates and rates of annual decline as well as risk factors for 427,111 births of which 12,181 were stillbirths. RESULTS: The mean stillbirth rates for the sites were 21.3 per 1000 births for Africa, 25.3 per 1000 births for India, 56.9 per 1000 births for Pakistan and 19.9 per 1000 births for Guatemala. From 2010 to 2016, across all sites, the mean stillbirth rate declined from 31.7 per 1000 births to 26.4 per 1000 births for an average annual decline of 3.0%. Risk factors for stillbirth were similar across the sites and included maternal age < 20 years and age > 35 years. Compared to parity 1-2, zero parity and parity > 3 were both associated with increased stillbirth risk and compared to women with any prenatal care, women with no prenatal care had significantly increased risk of stillbirth in all sites. CONCLUSIONS: At the current rates of decline, stillbirth rates in these sites will not reach the Every Newborn Action Plan goal of 12 per 1000 births by 2030. More attention to the risk factors and treating the causes of stillbirths will be required to reach the Every Newborn Action Plan goal of stillbirth reduction. TRIAL REGISTRATION: NCT01073475 .

A prospective study of maternal, fetal and neonatal outcomes in the setting of cesarean section in low- and middle-income countries.

INTRODUCTION: Cesarean section (CS) rates are increasing globally with an unclear effect on pregnancy outcomes. The study objective was to quantify maternal and perinatal morbidity and mortality associated with CS compared with vaginal delivery (VD) both within and across sites in low- and middle-income countries. MATERIAL AND METHODS: A prospective population-based study including home and facility births in 337 153 women with a VD and 47 308 women with a CS from 2010 to 2015 was performed in Guatemala, India, Kenya, Pakistan, Zambia and Democratic Republic of Congo. Women were enrolled during pregnancy; delivery and 6-week follow-up data were collected. RESULTS: Across all sites, CS rates increased from 8.6% to 15.2%, but remained low in African sites. Younger, nulliparous women were more likely to have a CS, as were women with higher education and those delivering an infant weighing 1500-2499 g. Across all sites, maternal and neonatal mortality was higher, and stillbirths were lower, in pregnancies delivered by CS. Antepartum and postpartum complications as well as obstetric interventions and treatments were more common among women who underwent CS. In stratified analyses, all outcomes were worse in women with a CS compared with VD in African compared to non-African sites. CONCLUSIONS: CS rates increased across all sites during the study period, but at more pronounced rates in the non-African sites. CS was associated with reduced postpartum hemorrhage and lower rates of stillbirths in the non-African sites. In the African sites, CS was associated with an increase in all adverse outcomes. Further studies are necessary to better understand the increase in adverse outcomes with CS in the African sites.

Anthropometric indices for non-pregnant women of childbearing age differ widely among four low-middle income populations.

BACKGROUND: Maternal stature and body mass indices (BMI) of non-pregnant women (NPW) of child bearing age are relevant to maternal and offspring health. The objective was to compare anthropometric indices of NPW in four rural communities in low- to low-middle income countries (LMIC). METHODS: Anthropometry and maternal characteristics/household wealth questionnaires were obtained for NPW enrolled in the Women First Preconception Maternal Nutrition Trial. Body mass index (BMI, kg/m2) was calculated. Z-scores were determined using WHO reference data. RESULTS: A total of 7268 NPW participated in Equateur, DRC (n = 1741); Chimaltenango, Guatemala (n = 1695); North Karnataka, India (n = 1823); and Thatta, Sindh, Pakistan (n = 2009). Mean age was 23 y and mean parity 1.5. Median (P25-P75) height (cm) ranged from 145.5 (142.2-148.9) in Guatemala to 156.0 (152.0-160.0) in DRC. Median weight (kg) ranged from 44.7 (39.9-50.3) in India to 52.7 (46.9-59.8) in Guatemala. Median BMI ranged from 19.4 (17.6-21.9) in India to 24.9 (22.3-28.0) in Guatemala. Percent stunted (<-2SD height for age z-score) ranged from 13.9% in DRC to 80.5% in Guatemala; % underweight (BMI <18.5) ranged from 1.2% in Guatemala to 37.1% in India; % overweight/obese (OW, BMI ≥25.0) ranged from 5.7% in DRC to 49.3% in Guatemala. For all sites, indicators for higher SES and higher age were associated with BMI. Lower SES women were underweight more frequently and higher SES women were OW more frequently at all sites. Younger women tended to be underweight, while older women tended to be OW. CONCLUSIONS: Anthropometric data for NPW varied widely among low-income rural populations in four countries located on three different continents. Global comparisons of anthropometric measurements across sites using standard reference data serve to highlight major differences among populations of low-income rural NPW and assist in evaluating the rationale for and the design of optimal intervention trials. TRIAL REGISTRATION: ClinicalTrials.gov # NCT01883193 (18 June 2013, retrospectively registered).