Nutritional support and prophylaxis of azithromycin for pregnant women to improve birth outcomes in peri-urban slums of Karachi, Pakistan—a protocol of multi-arm assessor-blinded randomized controlled trial (Mumta PW trial)

Background Maternal undernutrition is critical in the etiology of poor perinatal outcomes and accounts for 20% of small-for-gestational-age (SGA) births. High levels of food insecurity, antenatal undernourishment, and childhood undernutrition necessitate the supplementation of fortified balanced energy protein (BEP) during pregnancy in low-income settings especially with scarce literature available in this subject. Hence, this paper extensively covers the protocol of such a trial conducted in an urban slum of Karachi, Pakistan. Methods The trial is community-based, open-labelled, four-arm, and randomized controlled that will include parallel group assignments with a 1:1:1:1 allocation ratio in low-income squatter settlements in urban Karachi, Pakistan. All pregnant women (PW), if identified between > 8 and < 19 weeks of gestation based on ultrasound, will be offered routine antenatal care (ANC) counseling and voluntary participation in the trial after written informed consent. A total number of 1836 PW will be enrolled with informed consent and randomly allocated to one of the four arms receiving: (1) ANC counseling only (control group), (2) ANC counseling plus BEP supplement (intervention arm 1), (3) ANC counseling plus BEP supplement plus 2 doses azithromycin (intervention arm 2), or (4) ANC counseling plus BEP supplement plus daily single dose of nicotinamide and choline (intervention arm 3). Trial registration ClinicalTrials.govNCT04012177. Registered on July 9, 2019.

Epigenetics in the Uterine Environment: How Maternal Diet and ART May Influence the Epigenome in the Offspring with Long-Term Health Consequences

The societal burden of non-communicable disease is closely linked with environmental exposures and lifestyle behaviours, including the adherence to a poor maternal diet from the earliest preimplantation period of the life course onwards. Epigenetic variations caused by a compromised maternal nutritional status can affect embryonic development. This review summarises the main epigenetic modifications in mammals, especially DNA methylation, histone modifications, and ncRNA. These epigenetic changes can compromise the health of the offspring later in life. We discuss different types of nutritional stressors in human and animal models, such as maternal undernutrition, seasonal diets, low-protein diet, high-fat diet, and synthetic folic acid supplement use, and how these nutritional exposures epigenetically affect target genes and their outcomes. In addition, we review the concept of thrifty genes during the preimplantation period, and some examples that relate to epigenetic change and diet. Finally, we discuss different examples of maternal diets, their effect on outcomes, and their relationship with assisted reproductive technology (ART), including their implications on epigenetic modifications.

Nutritional Support and Prophylaxis of Azithromycin for Pregnant Women to Improve Birth Outcomes in Peri-Urban Slums of Karachi, Pakistan – A Protocol of Multi-arm Assessor Blinded Randomized Controlled Trial (Mumta PW Trial)

BackgroundMaternal undernutrition is critical in the etiology of poor perinatal outcomes and accounts for 20% of small-for-gestational-age (SGA) births. High levels of food insecurity, antenatal undernourishment and childhood undernutrition necessitate the supplementation of fortified balanced energy-protein (BEP) during pregnancy in low-income settings especially with scarce literature available in this subject. Hence, this paper extensively covers the protocol of such a trial conducted in an urban slum of Karachi, Pakistan. Methods The trial is community-based, open-labelled, four-arm, and randomized controlled that will include parallel group assignments with a 1:1:1:1 allocation ratio in low-income squatter settlements in urban Karachi, Pakistan. All pregnant women (PW), if identified between > 8 and <19 weeks of gestation based on ultrasound, will be offered routine antenatal care (ANC) counseling and voluntary participation in the trial after written informed consent. A total number of 1836 PW will be enrolled with informed consent and randomly allocated to one of the four arms receiving: (1) ANC counseling only (control group), (2) ANC counseling plus BEP supplement (intervention arm 1), (3) ANC counseling plus BEP supplement plus 2 doses Azithromycin (intervention arm 2), or (4) ANC counseling plus BEP supplement plus daily single dose of Nicotinamide and Choline (intervention arm 3). Trial Registration ClinicalTrials.gov NCT04012177. Registered on July 9, 2019. (https://clinicaltrials.gov/ct2/show/NCT04012177)

Scoping Review of Intervention Strategies for Improving Coverage and Uptake of Maternal Nutrition Services in Southeast Asia

Maternal undernutrition can lead to protein-energy malnutrition, micronutrient deficiencies, or anemia during pregnancy or after birth. It remains a major problem, despite evidence-based maternal-nutrition interventions happening on ground. We conducted a scoping review to understand different strategies and delivery mechanisms to improve maternal nutrition, as well as how interventions have improved coverage and uptake of services. An electronic search was conducted in PubMed and Google Scholar for published studies reporting on the effectiveness of maternal-nutrition interventions in terms of access or coverage, health outcomes, compliance, and barriers to intervention utilization. The search was limited to studies published within ten years before the initial search date, 8 November 2019; later, it was updated to 17 February 2021. Of 31 studies identified following screening and data extraction, 22 studies were included for narrative synthesis. Twelve studies were reported from India and eleven from Bangladesh, three from Nepal, two from both Pakistan and Thailand (Myanmar), and one from Indonesia. Nutrition education and counselling, home visits, directly observed supplement intake, community mobilization, food, and conditional cash transfer by community health workers were found to be effective. There is a need to incorporate diverse strategies, including various health education approaches, supplementation, as well as strengthening of community participation and the response of the health system in order to achieve impactful maternal nutrition programs.

Severe Gestational Low-Protein Intake Impacts Hippocampal Cellularity, Tau, and Amyloid-β Levels, and Memory Performance in Male Adult Offspring: An Alzheimer-Simile Disease Model?

Background: Maternal undernutrition has been associated with psychiatric and neurological disorders characterized by learning and memory impairment. Objective: Considering the lack of evidence, we aimed to analyze the effects of gestational protein restriction on learning and memory function associated with hippocampal cell numbers and neurodegenerative protein content later in life. Methods: Experiments were conducted in gestational low- (LP, 6% casein) or regular-protein (NP, 17% casein) diet intake offspring. Behavioral tests, isolated hippocampal isotropic fractionator cell studies, immunoblotting, and survival lifetime were observed. Results: The birthweight of LP males is significantly reduced relative to NP male progeny, and hippocampal mass increased in 88-week-old LP compared to age-matched NP offspring. The results showed an increased proximity measure in 87-week-old LP compared to NP offspring. Also, LP rats exhibited anxiety-like behaviors compared to NP rats at 48 and 86-wk of life. The estimated neuron number was unaltered in LP rats; however, non-neuron cell numbers increased compared to NP progeny. Here, we showed unprecedented hippocampal deposition of brain-derived neurotrophic factor, amyloid-β peptide (Aβ), and tau protein in 88-week-old LP relative to age-matched NP offspring. Conclusion: To date, no predicted studies showed changes in hippocampal morphological structure in maternal protein-restricted elderly offspring. The current data suggest that gestational protein restriction may accelerate hippocampal function loss, impacting learning/memory performance, and supposedly developing diseases similar to Alzheimer’s disease (AD) in elderly offspring. Thus, we propose that maternal protein restriction could be an elegant and novel method for constructing an AD-like model in adult male offspring.

When idiopathic male infertility is rooted in maternal malnutrition during the perinatal period in mice

Infertility represents a growing burden worldwide, with one in seven couples presenting difficulties conceiving. Amongst these, 10–15% of the men have idiopathic infertility that does not correlate with any defect in the classical sperm parameters measured. In the present study, we used a mouse model to investigate the effects of maternal undernutrition on fertility in male progeny. Our results indicate that mothers fed on a low protein diet during gestation and lactation produce male offspring with normal sperm morphology, concentration and motility but exhibiting an overall decrease of fertility when they reach adulthood. Particularly, in contrast to control, sperm from these offspring show a remarkable lower capacity to fertilize oocytes when copulation occurs early in the estrus cycle relative to ovulation, due to an altered sperm capacitation. Our data demonstrate for the first time that maternal nutritional stress can have long-term consequences on the reproductive health of male progeny by affecting sperm physiology, especially capacitation, with no observable impact on spermatogenesis and classical quantitative and qualitative sperm parameters. Moreover, our experimental model could be of major interest to study, explain, and ultimately treat certain categories of infertilities.

A comparative analysis of determinants of low birth weight and stunting among under five children of adolescent and non-adolescent mothers using 2015/16 Tanzania Demographic and Health Survey (TDHS)

Background Tanzania is one of the Sub-Saharan African country with nearly 12 out of 60 million people being adolescent. The prevalence of child marriage is higher with one out of every three girls being married before reaching their 18th birthday, 5 % being married by the age of 15, and 31% by the age of 18 years. Literature shows early pregnancy is associated with Low Birth Weight (LBW) and stunting among children under 5 years. This paper explores variation and factors associated with low birth weight and stunting among children born by adolescent and non-adolescent mothers. Methods Data from 13,266 women with children under 5 years collected as part of the 2015/2016 TDHS was re-analyzed using STATA version 14 software while accounting for survey design. A total of 6385 women (of which 7.2% were adolescent) and 8852 women (of which 6.7% were adolescent) were involved in the analysis of child birth weight and stunting respectively. Descriptive statistics stratified by maternal age was conducted with LBW and stunting as outcome variables followed by logistic regressions models controlling for confounding variables. Results The proportion of obese or overweight adolescent and non-adolescent mothers was 11.8 and 36.5% respectively. Antenatal care (ANC) attendance, areas of residence and social economic status were very similar in the two maternal age groups. Non- adolescent mothers had reduced odds of giving birth to LBW babies compared to adolescent mothers (Adjusted Odds Ratio (AOR) = 0.34; 95% CI: 0.22–0.50). Maternal undernutrition (AOR = 2.29; 95% CI: 1.43–3.67), being divorced, separated or widowed (AOR = 1.76; 95% CI: 1.24–2.50) and having at least four ANC visits (AOR = 0.64; 95% CI: 0.49–0.83) were significantly associated with reduced odds of having a LBW. Child stunting was not associated with maternal age. Maternal high socioeconomic status (AOR = 0.69; 95% CI: 0.57–0.84) and maternal obesity or overweight (AOR = 0.77; 95% CI: 0.64–0.92) were negatively associated with stunting. Child birth weight, sex, and age were significantly associated with stunting. Conclusion Maternal age was a predictor of LBW but not stunting. ANC attendance and not living with a spouse increase the risk of LBW babies. Stunting was associated with low maternal body mass index (BMI), low socioeconomic status, child birth weight, gender, and age. A multi-sectoral approach is needed to address child nutrition problems with teenagers ‘specific intervention that offer emotional support, and health education during pregnancies for improving immediate and later life child birth outcomes.

Maternal Nutrition and Neurodevelopment: A Scoping Review

In this scoping review, we examined the association between maternal nutrition during pregnancy and neurodevelopment in offspring. We searched the Pubmed and ScienceDirect databases for articles published from 2000 to 2020 on inadequate intake of vitamins (B12, folate, vitamin D, vitamin A, vitamin E, vitamin K), micronutrients (cooper, iron, creatine, choline, zinc, iodine), macronutrients (fatty acids, proteins), high fat diets, ketogenic diets, hypercaloric diets, and maternal undernutrition. Some older relevant articles were included. The search produced a total of 3590 articles, and 84 studies were included in the qualitative synthesis. Data were extracted and analyzed using charts and the frequency of terms used. We concluded that inadequate nutrient intake during pregnancy was associated with brain defects (diminished cerebral volume, spina bifida, alteration of hypothalamic and hippocampal pathways), an increased risk of abnormal behavior, neuropsychiatric disorders (ASD, ADHD, schizophrenia, anxiety, depression), altered cognition, visual impairment, and motor deficits. Future studies should establish and quantify the benefits of maternal nutrition during pregnancy on neurodevelopment and recommend adequate supplementation.