Neurocognitive outcomes in Malawian children exposed to malaria during pregnancy: An observational birth cohort study

BackgroundAnnually 125 million pregnancies are at risk of malaria infection. However, the impact of exposure to malaria in pregnancy on neurodevelopment in children is not well understood. We hypothesized that malaria in pregnancy and associated maternal immune activation result in neurodevelopmental delay in exposed offspring.Methods and findingsBetween April 2014 and April 2015, we followed 421 Malawian mother–baby dyads (median [IQR] maternal age: 21 [19, 28] years) who were previously enrolled (median [IQR] gestational age at enrollment: 19.7 [17.9, 22.1] weeks) in a randomized controlled malaria prevention trial with 5 or 6 scheduled assessments of antenatal malaria infection by PCR. Children were evaluated at 12, 18, and/or 24 months of age with cognitive tests previously validated in Malawi: the Malawi Developmental Assessment Tool (MDAT) and the MacArthur–Bates Communicative Development Inventories (MCAB-CDI). We assessed the impact of antenatal malaria (n [%] positive: 240 [57.3]), placental malaria (n [%] positive: 112 [29.6]), and maternal immune activation on neurocognitive development in children. Linear mixed-effects analysis showed that children exposed to antenatal malaria between 33 and 37 weeks gestation had delayed language development across the 2-year follow-up, as measured by MCAB-CDI (adjusted beta estimate [95% CI], −7.53 [−13.04, −2.02], p = 0.008). Maternal immune activation, characterized by increased maternal sTNFRII concentration, between 33 and 37 weeks was associated with lower MCAB-CDI language score (adjusted beta estimate [95% CI], −8.57 [−13.09, −4.06], p < 0.001). Main limitations of this study include a relatively short length of follow-up and a potential for residual confounding that is characteristic of observational studies.ConclusionsThis mother–baby cohort presents evidence of a relationship between malaria in pregnancy and neurodevelopmental delay in offspring. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental injury independent of birth weight or prematurity. Successful interventions to prevent malaria during pregnancy may reduce the risk of neurocognitive delay in children.

Andrea Weckman and co-workers study associations between children’s neurodevelopmental outcomes and malaria in pregnancy.     

The Impact of Food and Nutrient-Based Standards on Primary School Children’s Lunch and Total Dietary Intake: A Natural Experimental Evaluation of Government Policy in England

In 2005, the nutritional content of children’s school lunches in England was widely criticised, leading to a major policy change in 2006. Food and nutrient-based standards were reintroduced requiring primary schools to comply by September 2008. We aimed to determine the effect of the policy on the nutritional content at lunchtime and in children’s total diet. We undertook a natural experimental evaluation, analysing data from cross-sectional surveys in 12 primary schools in North East England, pre and post policy. Dietary data were collected on four consecutive days from children aged 4–7 years (n = 385 in 2003–4; n = 632 in 2008–9). We used linear mixed effect models to analyse the effects of gender, year, and lunch type on children’s mean total daily intake. Both pre- and post-implementation, children who ate a school lunch consumed less sodium (mean change −128 mg, 95% CI: −183 to −73 mg) in their total diet than children eating home-packed lunches. Post-implementation, children eating school lunches consumed a lower % energy from fat (−1.8%, −2.8 to −0.9) and saturated fat (−1.0%; −1.6 to −0.5) than children eating packed lunches. Children eating school lunches post implementation consumed significantly more carbohydrate (16.4 g, 5.3 to 27.6), protein (3.6 g, 1.1 to 6.0), non-starch polysaccharides (1.5 g, 0.5 to 1.9), vitamin C (0.7 mg, 0.6 to 0.8), and folate (12.3 µg, 9.7 to 20.4) in their total diet than children eating packed lunches. Implementation of school food policy standards was associated with significant improvements in the nutritional content of school lunches; this was reflected in children’s total diet. School food- and nutrient-based standards can play an important role in promoting dietary health and may contribute to tackling childhood obesity. Similar policy measures should be considered for other environments influencing children’s diet.     

Effects of Antenatal Maternal Depression and Anxiety on Children’s Early Cognitive Development: A Prospective Cohort Study

Introduction

Studies have shown that depression or anxiety occur in 10–20% of pregnant women. These disorders are often undertreated and may affect mothers and children’s health. This study investigates the relation between antenatal maternal depression, anxiety and children’s early cognitive development among 1380 two-year-old children and 1227 three-year-old children.

Methods

In the French EDEN Mother-Child Cohort Study, language ability was assessed with the Communicative Development Inventory at 2 years of age and overall development with the Ages and Stages Questionnaire at 3 years of age. Multiple regressions and structural equation modeling were used to examine links between depression, anxiety during pregnancy and child cognitive development.

Results

We found strong significant associations between maternal antenatal anxiety and poorer children’s cognitive development at 2 and 3 years. Antenatal maternal depression was not associated with child development, except when antenatal maternal anxiety was also present. Both postnatal maternal depression and parental stimulation appeared to play mediating roles in the relation between antenatal maternal anxiety and children’s cognitive development. At 3 years, parental stimulation mediated 13.2% of the effect of antenatal maternal anxiety while postnatal maternal depression mediated 26.5%.

Discussion

The partial nature of these effects suggests that other mediators may play a role. Implications for theory and research on child development are discussed.     

Estimating the Inbreeding Depression on Cognitive Behavior: A Population Based Study of Child Cohort

BackgroundCognitive ability tests are widely assumed to measure maximal intellectual performance and predictive associations between intelligence quotient (IQ) scores and later mental health problems. Very few epidemiologic studies have been done to demonstrate the relationship between familial inbreeding and modest cognitive impairments in children.ObjectiveWe aimed to estimate the effect of inbreeding on children’s cognitive behavior in comparison with non-inbred children.MethodologyA cohort of 408 children (6 to 15 years of age) was selected from inbred and non-inbred families of five Muslim populations of Jammu region. The Wechsler Intelligence Scales for Children (WISC) was used to measure the verbal IQ (VIQ), performance IQ (PIQ) and full scale IQ (FSIQ). Family pedigrees were drawn to access the family history and children’s inbred status in terms of coefficient of inbreeding (F).ResultsWe found significant decline in child cognitive abilities due to inbreeding and high frequency of mental retardation among offspring from inbred families. The mean differences (95% C.I.) were reported for the VIQ, being −22.00 (−24.82, −19.17), PIQ −26.92 (−29.96, −23.87) and FSIQ −24.47 (−27.35, −21.59) for inbred as compared to non-inbred children (p>0.001). The higher risk of being mentally retarded was found to be more obvious among inbred categories corresponding to the degree of inbreeding and the same accounts least for non-inbred children (p<0.0001). We observed an increase in the difference in mean values for VIQ, PIQ and FSIQ with the increase of inbreeding coefficient and these were found to be statistically significant (p<0.05). The regression analysis showed a fitness decline (depression) for VIQ (R² = 0.436), PIQ (R² = 0.468) and FSIQ (R² = 0.464) with increasing inbreeding coefficients (p<0.01).ConclusionsOur comprehensive assessment provides the evidence for inbreeding depression on cognitive abilities among children.     

Associations of maternal dietary inflammatory potential and quality with offspring birth outcomes: An individual participant data pooled analysis of 7 European cohorts in the ALPHABET consortium

BackgroundAdverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth outcomes. However, evidence on whole diet that considers complex nutrient and food interaction is rare and conflicting. We aim to elucidate the influence of whole-diet maternal dietary inflammatory potential and quality during periconceptional and antenatal periods on birth outcomes.Methods and findingsWe harmonized and pooled individual participant data (IPD) from up to 24,861 mother–child pairs in 7 European mother–offspring cohorts [cohort name, country (recruitment dates): ALSPAC, UK (1 April 1991 to 31 December 1992); EDEN, France (27 January 2003 to 6 March 2006); Generation R, the Netherlands (1 April 2002 to 31 January 2006); Lifeways, Ireland (2 October 2001 to 4 April 2003); REPRO_PL, Poland (18 September 2007 to 16 December 2011); ROLO, Ireland (1 January 2007 to 1 January 2011); SWS, United Kingdom (6 April 1998 to 17 December 2002)]. Maternal diets were assessed preconceptionally (n = 2 cohorts) and antenatally (n = 7 cohorts). Maternal dietary inflammatory potential and quality were ranked using the energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) index, respectively. Primary outcomes were birth weight and gestational age at birth. Adverse birth outcomes, i.e., low birth weight (LBW), macrosomia, small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm and postterm births were defined according to standard clinical cutoffs. Associations of maternal E-DII and DASH scores with infant birth outcomes were assessed using cohort-specific multivariable regression analyses (adjusted for confounders including maternal education, ethnicity, prepregnancy body mass index (BMI), maternal height, parity, cigarettes smoking, and alcohol consumption), with subsequent random-effects meta-analyses.Overall, the study mothers had a mean ± SD age of 29.5 ± 4.9 y at delivery and a mean BMI of 23.3 ± 4.2 kg/m². Higher pregnancy DASH score (higher dietary quality) was associated with higher birth weight [β(95% CI) = 18.5(5.7, 31.3) g per 1-SD higher DASH score; P value = 0.005] and head circumference [0.03(0.01, 0.06) cm; P value = 0.004], longer birth length [0.05(0.01, 0.10) cm; P value = 0.010], and lower risk of delivering LBW [odds ratio (OR) (95% CI) = 0.89(0.82, 0.95); P value = 0.001] and SGA [0.87(0.82, 0.94); P value < 0.001] infants. Higher maternal prepregnancy E-DII score (more pro-inflammatory diet) was associated with lower birth weight [β(95% CI) = −18.7(−34.8, −2.6) g per 1-SD higher E-DII score; P value = 0.023] and shorter birth length [−0.07(−0.14, −0.01) cm; P value = 0.031], whereas higher pregnancy E-DII score was associated with a shorter birth length [−0.06(−0.10, −0.01) cm; P value = 0.026] and higher risk of SGA [OR(95% CI) = 1.18(1.11, 1.26); P value < 0.001]. In male, but not female, infants higher maternal prepregnancy E-DII was associated with lower birth weight and head circumference, shorter birth length, and higher risk of SGA (P-for-sex-interaction = 0.029, 0.059, 0.104, and 0.075, respectively). No consistent associations were observed for maternal E-DII and DASH scores with gestational age, preterm and postterm birth, or macrosomia and LGA. Limitations of this study were that self-reported dietary data might have increased nondifferential measurement error and that causality cannot be claimed definitely with observational design.ConclusionsIn this cohort study, we observed that maternal diet that is of low quality and high inflammatory potential is associated with lower offspring birth size and higher risk of offspring being born SGA in this multicenter meta-analysis using harmonized IPD. Improving overall maternal dietary pattern based on predefined criteria may optimize fetal growth and avert substantial healthcare burden associated with adverse birth outcomes.

In this cohort analysis, Ling-Wei Chen and colleagues explore associations of maternal dietary patterns with offspring birth outcomes.     

Effectiveness of a brief group behavioral intervention for common mental disorders in Syrian refugees in Jordan: A randomized controlled trial

BackgroundCommon mental disorders are frequently experienced by refugees. This study evaluates the impact of a brief, lay provider delivered group-based psychological intervention [Group Problem Management Plus (gPM+)] on the mental health of refugees in a camp, as well as on parenting behavior and children’s mental health.Methods and findingsIn this single-blind, parallel, randomized controlled trial, 410 adult Syrian refugees (300 females, 110 males) in Azraq Refugee Camp (Jordan) were identified through screening of psychological distress (≥16 on the Kessler Psychological Distress Scale) and impaired functioning (≥17 on the WHO Disability Assessment Schedule). Participants were randomly allocated to gPM+ or enhanced usual care (EUC) involving referral information for psychosocial services on a 1:1 ratio. Participants were aware of treatment allocation, but assessors were blinded to treatment condition. Primary outcomes were scores on the Hopkins Symptom Checklist-25 (HSCL; depression and anxiety scales) assessed at baseline, 6 weeks, and 3 months follow-up as the primary outcome time point. It was hypothesized that gPM+ would result in greater reductions of scores on the HSCL than EUC. Secondary outcomes were disability, posttraumatic stress, personally identified problems, prolonged grief, prodromal psychotic symptoms, parenting behavior, and children’s mental health. Between October 15, 2019 and March 2, 2020, 624 refugees were screened for eligibility, 462 (74.0%) screened positive, of whom 204 were assigned to gPM+ and 206 to EUC. There were 168 (82.4%) participants in gPM+ and 189 (91.7%) in EUC assessed at follow-up. Intent-to-treat analyses indicated that at follow-up, participants in gPM+ showed greater reduction on HSCL depression scale than those receiving EUC (mean difference, 3.69 [95% CI 1.90 to 5.48], p = .001; effect size, 0.40). There was no difference between conditions in anxiety (mean difference −0.56, 95% CI −2.09 to 0.96; p = .47; effect size, −0.03). Relative to EUC, participants in gPM+ had greater reductions in severity of personally identified problems (mean difference 0.88, 95% CI 0.07 to 1.69; p = .03), and inconsistent disciplinary parenting (mean difference 1.54, 95% CI 1.03 to 2.05; p < .001). There were no significant differences between conditions for changes in PTSD, disability, grief, prodromal symptoms, or childhood mental health outcomes. Mediation analysis indicated the change in inconsistent disciplinary parenting was associated with reduced attentional (β = 0.11, SE .07; 95% CI .003 to .274) and internalizing (β = 0.08, SE .05; 95% CI .003 to 0.19) problems in children. No adverse events were attributable to the interventions or the trial. Major limitations included only one-quarter of participants being male, and measures of personally identified problems, grief, prodromal psychotic symptoms, inconsistent parenting behavior, and children’s mental health have not been validated with Syrians.ConclusionsIn camp-based Syrian refugees, a brief group behavioral intervention led to reduced depressive symptoms, personally identified problems, and disciplinary parenting compared to usual care, and this may have indirect benefits for refugees’ children. The limited capacity of the intervention to reduce PTSD, disability, or children’s psychological problems points to the need for development of more effective treatments for refugees in camp settings.Trial registrationProspectively registered at Australian and New Zealand Clinical Trials Registry: ACTRN12619001386123.

Richard A. Bryant and colleagues evaluate effects of a lay provider-delivered intervention on adult Syrian refugees’ mental health, parenting behavior, and their children’s mental health.     

Persistent Associations between Maternal Prenatal Exposure to Phthalates on Child IQ at Age 7 Years

Background

Prior research reports inverse associations between maternal prenatal urinary phthalate metabolite concentrations and mental and motor development in preschoolers. No study evaluated whether these associations persist into school age.

Methods

In a follow up of 328 inner-city mothers and their children, we measured prenatal urinary metabolites of di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP), di-isobutyl phthalate (DiBP), di-2-ethylhexyl phthalate and diethyl phthalate in late pregnancy. The Wechsler Intelligence Scale for Children, 4th edition was administered at child age 7 years and evaluates four areas of cognitive function associated with overall intelligence quotient (IQ).

Results

Child full-scale IQ was inversely associated with prenatal urinary metabolite concentrations of DnBP and DiBP: b = −2.69 (95% confidence interval [CI] = −4.33, −1.05) and b = −2.69 (95% CI = −4.22, −1.16) per log unit increase. Among children of mothers with the highest versus lowest quartile DnBP and DiBP metabolite concentrations, IQ was 6.7 (95% CI = 1.9, 11.4) and 7.6 (95% CI = 3.2, 12.1) points lower, respectively. Associations were unchanged after control for cognition at age 3 years. Significant inverse associations were also seen between maternal prenatal metabolite concentrations of DnBP and DiBP and child processing speed, perceptual reasoning and working memory; DiBP and child verbal comprehension; and BBzP and child perceptual reasoning.

Conclusion

Maternal prenatal urinary metabolite concentrations measured in late pregnancy of DnBP and DiBP are associated with deficits in children’s intellectual development at age 7 years. Because phthalate exposures are ubiquitous and concentrations seen here within the range previously observed among general populations, results are of public health significance.     

Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized,double-blind,placebo-controlled trial

BackgroundStunting among children in low-resource settings is associated with enteric pathogen carriage and micronutrient deficiencies. Our goal was to test whether administration of scheduled antimicrobials and daily nicotinamide improved linear growth in a region with a high prevalence of stunting and enteric pathogen carriage.Methods and findingsWe performed a randomized, 2 × 2 factorial, double-blind, placebo-controlled trial in the area around Haydom, Tanzania. Mother–child dyads were enrolled by age 14 days and followed with monthly home visits and every 3-month anthropometry assessments through 18 months. Those randomized to the antimicrobial arm received 2 medications (versus corresponding placebos): azithromycin (single dose of 20 mg/kg) at months 6, 9, 12, and 15 and nitazoxanide (3-day course of 100 mg twice daily) at months 12 and 15. Those randomized to nicotinamide arm received daily nicotinamide to the mother (250 mg pills months 0 to 6) and to the child (100 mg sachets months 6 to 18). Primary outcome was length-for-age z-score (LAZ) at 18 months in the modified intention-to-treat group. Between September 5, 2017 and August 31, 2018, 1,188 children were randomized, of whom 1,084 (n = 277 placebo/placebo, 273 antimicrobial/placebo, 274 placebo/nicotinamide, and 260 antimicrobial/nicotinamide) were included in the modified intention-to-treat analysis. The study was suspended for a 3-month period by the Tanzanian National Institute for Medical Research (NIMR) because of concerns related to the timing of laboratory testing and the total number of serious adverse events (SAEs); this resulted in some participants receiving their final study assessment late. There was a high prevalence of stunting overall (533/1,084, 49.2%). Mean 18-month LAZ did not differ between groups for either intervention (mean LAZ with 95% confidence interval [CI]: antimicrobial: −2.05 CI −2.13, −1.96, placebo: −2.05 CI −2.14, −1.97; mean difference: 0.01 CI −0.13, 0.11, p = 0.91; nicotinamide: −2.06 CI −2.13, −1.95, placebo: −2.04 CI −2.14, −1.98, mean difference 0.03 CI −0.15, 0.09, p = 0.66). There was no difference in LAZ for either intervention after adjusting for possible confounders (baseline LAZ, age in days at 18-month measurement, ward, hospital birth, birth month, years of maternal education, socioeconomic status (SES) quartile category, sex, whether the mother was a member of the Datoga tribe, and mother’s height). Adverse events (AEs) and SAEs were overall similar between treatment groups for both the nicotinamide and antimicrobial interventions. Key limitations include the absence of laboratory measures of pathogen carriage and nicotinamide metabolism to provide context for the negative findings.ConclusionsIn this study, we observed that neither scheduled administration of azithromycin and nitazoxanide nor daily provision of nicotinamide was associated with improved growth in this resource-poor setting with a high force of enteric infections. Further research remains critical to identify interventions toward improved early childhood growth in challenging conditions.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03268902","term_id":"NCT03268902"}}NCT03268902.

In a randomized trial, Mark DeBoer and colleagues investigate the effect of antimicrobial and nicotinamide interventions on child growth.     

Comparison in Outcomes at Two-Years of Age of Very Preterm Infants Born in 2000, 2005 and 2010

ObjectiveTo investigate alteration in 2-year neurological/behavioral outcomes of very preterm infants born in a French level three neonatal intensive care unit.MethodsWe conducted a prospective, comparative study of very preterm infants born before 33 weeks’ gestation at 5-year intervals in 2000, 2005 and 2010 at Rouen University Hospital. Neonatal mortality/morbidities, ante- and neonatal treatments, and at age 2 years motor, cognitive and behavioral data were collected by standardized questionnaires.ResultsWe included 536 very preterm infants. Follow-up rates at two years old were 78% in 2000, 93% in 2005 and 92% in 2010 respectively. No difference in gestational age, birthweight, neonatal mortality/morbidities was observed except a decrease in low grade subependymal/intraventricular hemorrhages. Care modifications concerned use of antenatal magnesium sulfate, breast-feeding and post-natal corticosteroid therapy. Significant improvement in motor outcome and dramatic decrease in cerebral palsy rates (12% in 2000, 6% in 2005, 1% in 2010, p<0.001) were observed, as were improvements in feeding behavior. Although a non significant difference to better psychosocial behavior was reported, there was no difference in cognitive outcome.ConclusionsImprovement in neuromotor outcome and behavior was reported. This could be due to multiple modifications in care: including administration of magnesium sulfate to women at risk of preterm birth, increase in breast-feeding, decrease in low grade subependymal/intraventricular hemorrhages, and decrease in post-natal corticosteroid therapy, all of which require further investigation in other studies. Extended follow-up until school age is mandatory for better detection of cognitive, learning and behavioral disorders.     

Child wellbeing and income inequality in rich societies: ecological cross sectional study

Objectives To examine associations between child wellbeing and material living standards (average income), the scale of differentiation in social status (income inequality), and social exclusion (children in relative poverty) in rich developed societies.Design Ecological, cross sectional studies.Setting Cross national comparisons of 23 rich countries; cross state comparisons within the United States.Population Children and young people.Main outcome measures The Unicef index of child wellbeing and its components for rich countries; eight comparable measures for the US states and District of Columbia (teenage births, juvenile homicides, infant mortality, low birth weight, educational performance, dropping out of high school, overweight, mental health problems).Results The overall index of child wellbeing was negatively correlated with income inequality (r=−0.64, P=0.001) and percentage of children in relative poverty (r=−0.67, P=0.001) but not with average income (r=0.15, P=0.50). Many more indicators of child wellbeing were associated with income inequality or children in relative poverty, or both, than with average incomes. Among the US states and District of Columbia all indicators were significantly worse in more unequal states. Only teenage birth rates and the proportion of children dropping out of high school were lower in richer states.Conclusions Improvements in child wellbeing in rich societies may depend more on reductions in inequality than on further economic growth.     

Contribution of Risk Factors to Extremely,Very and Moderately Preterm Births – Register-Based Analysis of 1,390,742 Singleton Births

Background

Preterm birth, defined as birth occurring before 37 weeks gestation, is one of the most significant contributors to neonatal mortality and morbidity, with long-term adverse consequences for health, and cognitive outcome.

Objective

The aim of the present study was to identify risk factors of preterm birth (≤36+6 weeks gestation) among singleton births and to quantify the contribution of risk factors to socioeconomic disparities in preterm birth.

Methods

A retrospective population–based case-control study using data derived from the Finnish Medical Birth Register. A total population of singleton births in Finland from 1987−2010 (n = 1,390,742) was reviewed.

Results

Among all singleton births (n = 1,390,742), 4.6% (n = 63,340) were preterm (<37 weeks), of which 0.3% (n = 4,452) were classed as extremely preterm, 0.4% (n = 6,213) very preterm and 3.8% (n = 54,177) moderately preterm. Smoking alone explained up to 33% of the variation in extremely, very and moderately preterm birth incidence between high and the low socioeconomic status (SES) groups. Reproductive risk factors (placental abruption, placenta previa, major congenital anomaly, amniocentesis, chorionic villus biopsy, anemia, stillbirth, small for gestational age (SGA) and fetal sex) altogether explained 7.7−25.0% of the variation in preterm birth between SES groups.

Conclusions

Smoking explained about one third of the variation in preterm birth groups between SES groups whereas the contribution of reproductive risk factors including placental abruption, placenta previa, major congenital anomaly, amniocentesis, chorionic villus biopsy, anemia, stillbirth, SGA and fetal sex was up to one fourth.     

Did School Food and Nutrient-Based Standards in England Impact on 11–12Y Olds Nutrient Intake at Lunchtime and in Total Diet? Repeat Cross-Sectional Study

Introduction

In September 2009, middle and secondary schools in England were required to comply with food and nutrient-based standards for school food. We examined the impact of this policy change on children’s lunchtime and total dietary intake.

Methods

We undertook repeat cross-sectional surveys in six Northumberland middle schools in 1999–2000 and 2009–10. Dietary data were collected from 11–12 y olds (n = 298 in 1999–2000; n = 215 in 2009–10). Children completed two consecutive 3-day food diaries, each followed by an interview. Linear mixed effect models examined the effect of year, lunch type and level of socio-economic deprivation on children’s mean total dietary intake.

Results

We found both before and after the introduction of the food and nutrient-based standards children consuming a school lunch, had a lower per cent energy from saturated fat (−0.5%; p = 0.02), and a lower intake of sodium (−143 mg; p = 0.02), and calcium (−81 mg; p = 0.001) in their total diet, compared with children consuming a home-packed lunch. We found no evidence that lunch type was associated with mean energy, or absolute amounts of NSP, vitamin C and iron intake. There was marginal evidence of an association between lunch type and per cent energy NMES (p = 0.06). In 1999–2000, children consuming a school lunch had a higher per cent energy from fat in their total diet compared with children consuming a home-packed lunch (2.8%), whereas by 2009–10, they had slightly less (−0.2%) (year by lunch type interaction p<0.001; change in mean differences −3%).

Conclusions

We found limited evidence of an impact of the school food and nutrient-based standards on total diet among 11–12 year olds. Such policies may need to be supported by additional measures, including guidance on individual food choice, and the development of wider supportive environments in school and beyond the school gates.     

Induction of labour at 41 weeks or expectant management until 42 weeks: A systematic review and an individual participant data meta-analysis of randomised trials

BackgroundThe risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject.Methods and findingsWe searched PubMed, Excerpta Medica dataBASE (Embase), The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO on February 21, 2020 for RCTs comparing IOL at 41 weeks with expectant management until 42 weeks in women with uncomplicated pregnancies. Individual participant data (IPD) were sought from eligible RCTs. Primary outcome was a composite of severe adverse perinatal outcomes: mortality and severe neonatal morbidity. Additional outcomes included neonatal admission, mode of delivery, perineal lacerations, and postpartum haemorrhage. Prespecified subgroup analyses were conducted for parity (nulliparous/multiparous), maternal age (<35/≥35 years), and body mass index (BMI) (<30/≥30). Aggregate data meta-analysis (MA) was performed to include data from RCTs for which IPD was not available.From 89 full-text articles, we identified three eligible RCTs (n = 5,161), and two contributed with IPD (n = 4,561). Baseline characteristics were similar between the groups regarding age, parity, BMI, and higher level of education. IOL resulted overall in a decrease of severe adverse perinatal outcome (0.4% [10/2,281] versus 1.0% [23/2,280]; relative risk [RR] 0.43 [95% confidence interval [CI] 0.21 to 0.91], p-value 0.027, risk difference [RD] −57/10,000 [95% CI −106/10,000 to −8/10,000], I² 0%). The number needed to treat (NNT) was 175 (95% CI 94 to 1,267).Perinatal deaths occurred in one (<0.1%) versus eight (0.4%) pregnancies (Peto odds ratio [OR] 0.21 [95% CI 0.06 to 0.78], p-value 0.019, RD −31/10,000, [95% CI −56/10,000 to −5/10,000], I² 0%, NNT 326, [95% CI 177 to 2,014]) and admission to a neonatal care unit ≥4 days occurred in 1.1% (24/2,280) versus 1.9% (46/2,273), (RR 0.52 [95% CI 0.32 to 0.85], p-value 0.009, RD −97/10,000 [95% CI −169/10,000 to −26/10,000], I² 0%, NNT 103 [95% CI 59 to 385]). There was no difference in the rate of cesarean delivery (10.5% versus 10.7%; RR 0.98, [95% CI 0.83 to 1.16], p-value 0.81) nor in other important perinatal, delivery, and maternal outcomes. MA on aggregate data showed similar results.Prespecified subgroup analyses for the primary outcome showed a significant difference in the treatment effect (p = 0.01 for interaction) for parity, but not for maternal age or BMI. The risk of severe adverse perinatal outcome was decreased for nulliparous women in the IOL group (0.3% [4/1,219] versus 1.6% [20/1,264]; RR 0.20 [95% CI 0.07 to 0.60], p-value 0.004, RD −127/10,000, [95% CI −204/10,000 to −50/10,000], I² 0%, NNT 79 [95% CI 49 to 201]) but not for multiparous women (0.6% [6/1,219] versus 0.3% [3/1,264]; RR 1.59 [95% CI 0.15 to 17.30], p-value 0.35, RD 27/10,000, [95% CI −29/10,000 to 84/10,000], I² 55%).A limitation of this IPD-MA was the risk of overestimation of the effect on perinatal mortality due to early stopping of the largest included trial for safety reasons after the advice of the Data and Safety Monitoring Board. Furthermore, only two RCTs were eligible for the IPD-MA; thus, the possibility to assess severe adverse neonatal outcomes with few events was limited.ConclusionsIn this study, we found that, overall, IOL at 41 weeks improved perinatal outcome compared with expectant management until 42 weeks without increasing the cesarean delivery rate. This benefit is shown only in nulliparous women, whereas for multiparous women, the incidence of mortality and morbidity was too low to demonstrate any effect. The magnitude of risk reduction of perinatal mortality remains uncertain. Women with pregnancies approaching 41 weeks should be informed on the risk differences according to parity so that they are able to make an informed choice for IOL at 41 weeks or expectant management until 42 weeks.Study Registration: PROSPERO CRD42020163174

Mårten Alkmark and co-workers report on a meta-analysis of randomized trials of labour induction at 41 weeks'' gestation as compared with expectant management until 42 weeks.     

Associations between cesarean delivery and child mortality: A national record linkage longitudinal study of 17.8 million births in Brazil

BackgroundThere is an increasing use of cesarean delivery (CD) based on preference rather than on medical indication. However, the extent to which nonmedically indicated CD benefits or harms child survival remains unclear. Our hypothesis was that in groups with a low indication for CD, this procedure would be associated with higher child mortality and in groups with a clear medical indication CD would be associated with improved child survival chances.Methods and findingsWe conducted a population-based cohort study in Brazil by linking routine data on live births between January 1, 2012 and December 31, 2018 and assessing mortality up to 5 years of age. Women with a live birth who contributed records during this period were classified into one of 10 Robson groups based on their pregnancy and delivery characteristics. We used propensity scores to match CD with vaginal deliveries (1:1) and prelabor CD with unscheduled CD (1:1) and estimated associations with child mortality using Cox regressions. A total of 17,838,115 live births were analyzed. After propensity score matching (PSM), we found that live births to women in groups with low expected frequencies of CD (Robson groups 1 to 4) had a higher death rate up to age 5 years if they were born via CD compared with vaginal deliveries (HR = 1.25, 95% CI: 1.22 to 1.28; p < 0.001). The relative rate was greatest in the neonatal period (HR = 1.39, 95% CI: 1.34 to 1.45; p < 0.001). There was no difference in mortality rate when comparing offspring born by a prelabor CD to those born by unscheduled CD. For the live births to women with a CD in a prior pregnancy (Robson group 5), the relative rates for child mortality were similar for those born by CD compared with vaginal deliveries (HR = 1.05, 95% CI: 1.00 to 1.10; p = 0.024). In contrast, for live births to women in groups with high expected rates of CD (Robson groups 6 to 10), the child mortality rate was lower for CD than for vaginal deliveries (HR = 0.90, 95% CI: 0.89 to 0.91; p < 0.001), particularly in the neonatal period (HR = 0.84, 95% CI: 0.83 to 0.85; p < 0.001). Our results should be interpreted with caution in clinical practice, since relevant clinical data on CD indication were not available.ConclusionsIn this study, we observed that in Robson groups with low expected frequencies of CD, this procedure was associated with a 25% increase in child mortality. However, in groups with high expected frequencies of CD, the findings suggest that clinically indicated CD is associated with a reduction in child mortality.

In a study of linked population-based data, Enny Paixao and colleagues study the associations between cesarean section and child mortality among 17.8 million live births in Brazil.     

Reproductive health among married and unmarried mothers aged less than 18, 18–19, and 20–24 years in the United States, 2014–2019: A population-based cross-sectional study

BackgroundStudies in low- and middle-income regions suggest that child marriage (<18 years) is a risk factor for poor reproductive outcomes among women. However, in high-income-country contexts where childbearing before age 18 occurs predominantly outside marriage, it is unknown whether marriage is adversely associated with reproductive health among mothers below age 18. This study examined the joint associations of marriage and adolescent maternal age group (<18, 18–19, and 20–24 years) with reproductive, maternal, and infant health indicators in the United States.Methods and findingsBirth registrations with US resident mothers aged ≤24 years with complete information on marital status were drawn from the 2014 to 2019 Natality Public Use Files (n = 5,669,824). Odds ratios for the interaction between marital status and maternal age group were estimated using multivariable logistic regression, adjusting for covariates such as maternal race/ethnicity and nativity status, federal program participation, and paternal age. Marriage prevalence was 3.6%, 13.2%, and 34.1% among births to mothers aged <18, 18–19, and 20–24 years, respectively. Age gradients in the adjusted odds ratios (AORs) were present for most indicators, and many gradients differed by marital status. Among births to mothers aged <18 years, marriage was associated with greater adjusted odds of prior pregnancy termination (AOR 1.64, 95% CI 1.52–1.77, p < 0.001), repeat birth (AOR 2.84, 95% CI 2.68–3.00, p < 0.001), maternal smoking (AOR 1.24, 95% CI 1.15–1.35, p < 0.001), and infant morbidity (AOR 1.07, 95% CI 1.01–1.14, p = 0.03), but weaker or reverse associations existed among births to older mothers. For all maternal age groups, marriage was associated with lower adjusted odds of late or no prenatal care initiation, sexually transmitted infection, and no breastfeeding at hospital discharge, but these beneficial associations were weaker among births to mothers aged <18 and 18–19 years. Limitations of the study include its cross-sectional nature and lack of information on marriage timing relative to prior pregnancy events.ConclusionsMarriage among mothers below age 18 is associated with both adverse and favorable reproductive, maternal, and infant health indicators. Heterogeneity exists in the relationship between marriage and reproductive health across adolescent maternal age groups, suggesting girl child marriages must be examined separately from marriages at older ages.

In a population-based study, Andrée-Anne Fafard St-Germain and colleagues examine the joint associations of marriage and adolescent maternal age group (<18, 18-19, and 20-24 years) with reproductive, maternal, and infant health indicators in the United States.     

School performance in Danish children exposed to maternal type 1 diabetes in utero: A nationwide retrospective cohort study

BackgroundConflicting results have been reported concerning possible adverse effects on the cognitive function of offspring of mothers with type 1 diabetes (O-mT1D). Previous studies have included offspring of parents from the background population (O-BP), but not offspring of fathers with type 1 diabetes (O-fT1D) as the unexposed reference group.Methods and findingsThis is a population-based retrospective cohort study from 2010 to 2016. Nationally standardized school test scores (range, 1 to 100) were obtained for public school grades 2, 3, 4, 6, and 8 in O-mT1D and compared with those in O-fT1D and O-BP. Of the 622,073 included children, 2,144 were O-mT1D, and 3,474 were O-fT1D. Multiple linear regression models were used to compare outcomes, including the covariates offspring with type 1 diabetes, parity, number of siblings, offspring sex, smoking during pregnancy, parental age, and socioeconomic factors. Mean test scores were 54.2 (standard deviation, SD 24.8) in O-mT1D, 54.4 (SD 24.8) in O-fT1D, and 56.4 (SD 24.7) in O-BP. In adjusted analyses, the mean differences in test scores were −1.59 (95% CI −2.48 to −0.71, p < 0.001) between O-mT1D and O-BP and −0.78 (95% CI −1.48 to −0.08, p = 0.03) between O-fT1D and O-BP. No significant difference in the adjusted mean test scores was found between O-mT1D and O-fT1D (p = 0.16). The study’s limitation was no access to measures of glycemic control during pregnancy.ConclusionsO-mT1D achieved lower test scores than O-BP but similar test scores compared with O-fT1D. Glycemic control during pregnancy is essential to prevent various adverse pregnancy outcomes in women with type 1 diabetes. However, the present study reduces previous concerns regarding adverse effects of in utero hyperglycemia on offspring cognitive function.

Anne Lærke Spangmose and colleagues examine the association between school performance and exposure to maternal or paternal type 1 diabetes in utero in Denmark.     

Fetal DNA Methylation Associates with Early Spontaneous Preterm Birth and Gestational Age

Spontaneous preterm birth (PTB, <37 weeks gestation) is a major public health concern, and children born preterm have a higher risk of morbidity and mortality throughout their lives. Recent studies suggest that fetal DNA methylation of several genes varies across a range of gestational ages (GA), but it is not yet clear if fetal epigenetic changes associate with PTB. The objective of this study is to interrogate methylation patterns across the genome in fetal leukocyte DNA from African Americans with early PTB (24^1/7–34^0/7 weeks; N = 22) or term births (39^0/7–40^6/7weeks; N = 28) and to evaluate the association of each CpG site with PTB and GA. DNA methylation was assessed across the genome with the HumanMethylation450 BeadChip. For each individual sample and CpG site, the proportion of DNA methylation was estimated. The associations between methylation and PTB or GA were evaluated by fitting a separate linear model for each CpG site, adjusting for relevant covariates. Overall, 29 CpG sites associated with PTB (FDR<.05; 5.7×10⁻¹⁰<p<2.9×10⁻⁶) independent of GA. Also, 9637 sites associated with GA (FDR<.05; 9.5×10⁻¹⁶<p<1.0×10⁻³), with 61.8% decreasing in methylation with shorter GA. GA-associated CpG sites were depleted in the CpG islands of their respective genes (p<2.2×10⁻¹⁶). Gene set enrichment analysis (GSEA) supported enrichment of GA-associated CpG sites in genes that play a role in embryonic development as well as the extracellular matrix. Additionally, this study replicated the association of several CpG sites associated with gestational age in other studies (CRHBP, PIK3CD and AVP). Dramatic differences in fetal DNA methylation are evident in fetuses born preterm versus at term, and the patterns established at birth may provide insight into the long-term consequences associated with PTB.     

Parenting interventions to promote early child development in the first three years of life: A global systematic review and meta-analysis

BackgroundParents are the primary caregivers of young children. Responsive parent–child relationships and parental support for learning during the earliest years of life are crucial for promoting early child development (ECD). We conducted a global systematic review and meta-analysis to evaluate the effectiveness of parenting interventions on ECD and parenting outcomes.Methods and findingsWe searched MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and Global Health Library for peer-reviewed, published articles from database inception until November 15, 2020. We included randomized controlled trials (RCTs) of parenting interventions delivered during the first 3 years of life that evaluated at least 1 ECD outcome. At least 2 reviewers independently screened, extracted data, and assessed study quality from eligible studies. ECD outcomes included cognitive, language, motor, and socioemotional development, behavior problems, and attachment. Parenting outcomes included parenting knowledge, parenting practices, parent–child interactions, and parental depressive symptoms. We calculated intervention effect sizes as the standardized mean difference (SMD) and estimated pooled effect sizes for each outcome separately using robust variance estimation meta-analytic approaches. We used random-effects meta-regression models to assess potential effect modification by country-income level, child age, intervention content, duration, delivery, setting, and study quality. This review was registered with PROSPERO (CRD42018092458 and CRD42018092461). Of the 11,920 articles identified, we included 111 articles representing 102 unique RCTs. Pooled effect sizes indicated positive benefits of parenting interventions on child cognitive development (SMD = 0.32, 95% CI [confidence interval]: 0.23, 0.40, P < 0.001), language development (SMD = 0.28, 95% CI: 0.18 to 0.37, P < 0.001), motor development (SMD = 0.24, 95% CI: 0.15 to 0.32, P < 0.001), socioemotional development (SMD = 0.19, 95% CI: 0.10 to 0.28, P < 0.001), and attachment (SMD = 0.29, 95% CI: 0.18 to 0.40, P < 0.001) and reductions in behavior problems (SMD = −0.13, 95% CI: −0.18 to −0.08, P < 0.001). Positive benefits were also found on parenting knowledge (SMD = 0.56, 95% CI: 0.33 to 0.79, P < 0.001), parenting practices (SMD = 0.33, 95% CI: 0.22 to 0.44, P < 0.001), and parent–child interactions (SMD = 0.39, 95% CI: 0.24 to 0.53, P < 0.001). However, there was no significant reduction in parental depressive symptoms (SMD = −0.07, 95% CI: −0.16 to 0.02, P = 0.08). Subgroup analyses revealed significantly greater effects on child cognitive, language, and motor development, and parenting practices in low- and middle-income countries compared to high-income countries; and significantly greater effects on child cognitive development, parenting knowledge, parenting practices, and parent–child interactions for programs that focused on responsive caregiving compared to those that did not. On the other hand, there was no clear evidence of effect modification by child age, intervention duration, delivery, setting, or study risk of bias. Study limitations include considerable unexplained heterogeneity, inadequate reporting of intervention content and implementation, and varying quality of evidence in terms of the conduct of trials and robustness of outcome measures used across studies.ConclusionsParenting interventions for children during the first 3 years of life are effective for improving ECD outcomes and enhancing parenting outcomes across low-, middle-, and high-income countries. Increasing implementation of effective and high-quality parenting interventions is needed globally and at scale in order to support parents and enable young children to achieve their full developmental potential.

In a systematic review and meta-analysis, Joshua Jeong and colleagues study the effectiveness of parenting interventions in children 3 years and younger in promoting early childhood development and parenting outcomes.