Perinatal inflammation, fetal growth restriction, and long-term neurodevelopmental impairment in Bangladesh.

BACKGROUND: There are limited data on the impact of perinatal inflammation on child neurodevelopment in low-middle income countries and among growth-restricted infants. METHODS: Population-based, prospective birth cohort study of 288 infants from July 2016-March 2017 in Sylhet, Bangladesh. Umbilical cord blood was analyzed for interleukin(IL)-1α, IL-1ß, IL-6, IL-8, and C-reactive protein(CRP). Child neurodevelopment was assessed at 24 months with Bayley-III Scales of Infant Development. We determined associations between cord blood inflammation and neurodevelopmental outcomes, controlling for potential confounders. RESULTS: 248/288 (86%) live born infants were followed until 24 months, among whom 8.9% were preterm and 45.0% small-for-gestational-age(SGA) at birth. Among all infants, elevated concentrations (>75%) of CRP and IL-6 at birth were associated with increased odds of fine motor delay at 24 months; elevated CRP was also associated with lower receptive communication z-scores. Among SGA infants, elevated IL-1α was associated with cognitive delay, IL-8 with language delay, CRP with lower receptive communication z-scores, and IL-1ß with lower expressive communication and motor z-scores. CONCLUSIONS: In rural Bangladesh, perinatal inflammation was associated with impaired neurodevelopment at 24 months. The associations were strongest among SGA infants and noted across several biomarkers and domains, supporting the neurobiological role of inflammation in adverse fetal development, particularly in the setting of fetal growth restriction. IMPACT: Cord blood inflammation was associated with fine motor and language delays at 24 months of age in a community-based cohort in rural Bangladesh. 23.4 million infants are born small-for-gestational-age (SGA) globally each year. Among SGA infants, the associations between cord blood inflammation and adverse outcomes were strong and consistent across several biomarkers and neurodevelopmental domains (cognitive, motor, language), supporting the neurobiological impact of inflammation prominent in growth-restricted infants. Prenatal interventions to prevent intrauterine growth restriction are needed in low- and middle-income countries and may also result in long-term benefits on child development.

Urinary tract infections in pregnancy in a rural population of Bangladesh: population-based prevalence, risk factors, etiology, and antibiotic resistance.

BACKGROUND: Urinary tract infection (UTI) in pregnancy, including asymptomatic bacteriuria, is associated with maternal morbidity and adverse pregnancy outcomes, including preterm birth and low birthweight. In low-middle income countries (LMICs), the capacity for screening and treatment of UTIs is limited. The objective of this study was to describe the population-based prevalence, risk factors, etiology and antimicrobial resistance patterns of UTIs in pregnancy in Bangladesh. METHODS: In a community-based cohort in Sylhet district, Bangladesh, urine specimens were collected at the household level in 4242 pregnant women (< 20 weeks gestation) for culture and antibiotic susceptibility testing. Basic descriptive analysis was performed, as well as logistic regression to calculate adjusted odds ratios (aOR) for UTI risk factors. RESULTS: The prevalence of UTI was 8.9% (4.4% symptomatic UTI, 4.5% asymptomatic bacteriuria). Risk factors for UTI in this population included maternal undernutrition (mid-upper arm circumference <23 cm: aOR= 1.29, 95% CI: 1.03-1.61), primiparity (aOR= 1.45, 95% CI: 1.15-1.84), and low paternal education (no education: aOR= 1.56, 95% CI: 1.09-2.22). The predominant uro-pathogens were E. coli (38% of isolates), Klebsiella (12%), and staphyloccocal species (23%). Group B streptococcus accounted for 5.3% of uro-pathogens. Rates of antibiotic resistance were high, with only two-thirds of E. coli susceptible to 3rd generation cephalosporins. CONCLUSIONS: In Sylhet, Bangladesh, one in 11 women had a UTI in pregnancy, and approximately half of cases were asymptomatic. There is a need for low-cost and accurate methods for UTI screening in pregnancy and efforts to address increasing rates of antibiotic resistance in LMIC.

Family Involvement in the Routine Care of Hospitalized Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Preterm and low birth weight (LBW) infants are often separated from parents during hospitalization. Our objective was to assess effects of interventions to increase family involvement in the routine newborn care of preterm or LBW infants compared with standard NICU care on infant and parental outcomes. METHODS: Data sources include Medline, Embase, CINAHL, and World Health Organization Global Index Medicus to August 2021. The study selection included randomized controlled trials (RCTs) of family involvement intervention packages. Data were extracted and pooled with random-effects models. RESULTS: We included 15 RCTs with 5240 participants. All interventions included direct parental bedside care; packages varied with respect to additional components. Family involvement interventions decreased retinopathy of prematurity (odds ratio 0.52, 95% confidence interval [CI]: 0.34, 0.80; 8 RCTs), length of hospital stay (mean difference [MD] -2.91 days; 95% CI: -5.15,-0.82; 11 RCTs), and parental stress and anxiety (Parental Stress Scale: MD -0.29 points, 95% CI: -0.56,-0.01, 2 RCTs; Anxiety State-Trait scale: MD -1.79, 95% CI: -3.11,-0.48; 2 RCTs). Family involvement increased weight gain velocity (MD 2.09 g/day; 95% CI: 1.27, 2.91; 3 RCTs), neurobehavioral exam scores (MD: 1.11; 95% CI: 0.21, 2.01; 2 RCTs) and predominant or exclusive breastmilk intake (odds ratio 1.34; 95% CI: 1.01, 1.65; 3 RCTs). It may decrease rates of bronchopulmonary dysplasia, infection, and intraventricular hemorrhage. There were no effects on mortality or necrotizing enterocolitis. Certainty of evidence ranged from low to moderate. CONCLUSIONS: Family involvement has a beneficial role on several infant and parental outcomes.

Measurement of symphysis fundal height for gestational age estimation in low-to-middle-income countries: A systematic review and meta-analysis.

In low- and middle-income countries (LMIC), measurement of symphysis fundal height (SFH) is often the only available method of estimating gestational age (GA) in pregnancy. This systematic review aims to summarize methods of SFH measurement and assess the accuracy of SFH for the purpose of GA estimation. We searched PubMed, EMBASE, Cochrane, Web of Science, POPLINE, and WHO Global Health Libraries from January 1980 through November 2021. For SFH accuracy, we pooled the variance of the mean difference between GA confirmed by ultrasound versus SFH. Of 1,003 studies identified, 37 studies were included. Nineteen different SFH measurement techniques and 13 SFH-to-GA conversion methods were identified. In pooled analysis of five studies (n = 5838 pregnancies), 71% (95% CI: 66-77%) of pregnancies dated by SFH were within ±14 days of ultrasound confirmed dating. Using the 1 cm SFH = 1wk assumption, SFH underestimated GA compared with ultrasound-confirmed GA (mean bias: -14.0 days) with poor accuracy (95% limits of agreement [LOA]: ±42.8 days; n = 3 studies, 2447 pregnancies). Statistical modeling of three serial SFH measurements performed better, but accuracy was still poor (95% LOA ±33 days; n = 4 studies, 4391 pregnancies). In conclusion, there is wide variation in SFH measurement and SFH-to-GA conversion techniques. SFH is inaccurate for estimating GA and should not be used for GA dating. Increasing access to quality ultrasonography early in pregnancy should be prioritized to improve gestational age assessment in LMIC.

Diagnostic accuracy of neonatal foot length to identify preterm and low birthweight infants: a systematic review and meta-analysis.

INTRODUCTION: Eighty percent of neonatal deaths occur among babies born preterm and/or small for gestational age (SGA). In sub-Saharan Africa and South Asia, approximately 40% of births occur outside of health facilities, and gestational age (GA) and birth weight are commonly unknown. Foot length (FL) has been proposed as a simple, surrogate measurement to identify and triage small babies born in the community. We conducted a systematic review and meta-analysis of the diagnostic accuracy of newborn FL to classify preterm and low birthweight infants. METHODS: PubMed, EMBASE, Cochrane, Web of Science, POPLINE and WHO Global Health Library databases were searched. Studies of live-born infants that compared FL with GA and/or birth weight were included. Data on diagnostic accuracy were summarised, described, and pooled, as appropriate. RESULTS: Six hundred and two studies were identified and 41 included. Techniques for measuring FL included use of a firm plastic ruler, callipers, footprint or a measuring board. Twelve studies assessed the diagnostic accuracy of FL to identify preterm births; however, data were not pooled given heterogeneity and low quality of GA. 19 studies used FL to identify low birthweight infants (<2500 g, <2000 g). Among studies in Asia (n=3), FL <7.7 cm had pooled sensitivity and specificity of 87.6% (95% CI 61.1% to 99.0%) and 70.9% (95% CI 23.5% to 95.1%), respectively, to identify <2500 g infants. FL <7.3 cm had 82.1% (95% CI 63.7% to 92.2%) sensitivity and 82.1% (95% CI 59.2% to 90.8%) specificity for identifying <2000 g infants (n=3). In the African studies (n=3), FL <7.9 cm had pooled sensitivity and specificity of 92.0% (95% CI 85.6% to 95.7%) and 71.9% (95% CI 44.5% to 89.1%), respectively, to identify <2500 g neonates. CONCLUSIONS: FL is a simple proxy measure that can identify babies of low birthweight with high sensitivity, though somewhat lower specificity. Additional research is needed to determine the validity of FL to identify preterm infants, and understand the programmatic impact of screening on healthcare seeking and outcomes. PROSPERO REGISTRATION NUMBER: CRD42015020499.

A Novel Icterometer for Hyperbilirubinemia Screening in Low-Resource Settings.

BACKGROUND: Severe neonatal hyperbilirubinemia (>20 mg/dL) affects ∼1 million infants annually. Improved jaundice screening in low-income countries is needed to prevent bilirubin encephalopathy and mortality. METHODS: The Bili-ruler is an icterometer for the assessment of neonatal jaundice that was designed by using advanced digital color processing. A total of 790 newborns were enrolled in a validation study at Brigham and Women's Hospital (Boston) and Sylhet Osmani Medical College Hospital (Sylhet, Bangladesh). Independent Bili-ruler measurements were made and compared with reference standard transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) concentrations. RESULTS: Bili-ruler scores on the nose were correlated with TcB and TSB levels (r = 0.76 and 0.78, respectively). The Bili-ruler distinguished different clinical thresholds of hyperbilirubinemia, defined by TcB, with high sensitivity and specificity (score ≥3.5: 90.1% [95% confidence interval (CI): 84.8%-95.4%] and 85.9% [95% CI: 83.2%-88.6%], respectively, for TcB ≥13 mg/dL). The Bili-ruler also performed reasonably well compared to TSB (score ≥3.5: sensitivity 84.5% [95% CI: 79.1%-90.3%] and specificity 83.2% [95% CI: 76.1%-90.3%] for TSB ≥11 mg/dL). Areas under the receiver operating characteristic curve for identifying TcB ≥11, ≥13, and ≥15 were 0.92, 0.93, and 0.94, respectively, and 0.90, 0.87, and 0.86 for identifying TSB ≥11, ≥13, and ≥15. Interrater reliability was high; 97% of scores by independent readers fell within 1 score of one another (N = 88). CONCLUSIONS: The Bili-ruler is a low-cost, noninvasive tool with high diagnostic accuracy for neonatal jaundice screening. This device may be used to improve referrals from community or peripheral health centers to higher-level facilities with capacity for bilirubin testing and/or phototherapy.