Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

The effects of vitamin D supplementation on glycemic control and maternal-neonatal outcomes in women with established gestational diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND & AIMS: Gestational Diabetes Mellitus (GDM) is associated with a well-documented range of adverse pregnancy outcomes. The present meta-analysis was conducted to evaluate the effects of vitamin D supplementation on glycemic control and maternal-neonatal outcomes in women with established GDM. METHODS: Published literature was retrieved and screened from PubMed, Embase, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang, and Cochrane Center Register of Controlled Trails up to May 2020. RCTs of vitamin D supplementation on pregnant women with GDM were included. RESULTS: 19 RCTs (1550 participants) were eligible for meta-analyses. Overall, vitamin D supplementation significantly reduced serum fasting plasma glucose (FPG) (MD: -10.20 mg/dL, 95%CI: -13.43 to -6.96), insulin concentration (MD: -5.02 µIU/mL, 95%CI: -6.83 to -3.20) and the homeostasis model assessment of insulin resistance (HOMA-IR) (MD:-1.06, 95%CI: -1.40 to -0.72) in women with GDM. In addition, vitamin D supplementation in pregnant women with GDM significantly reduced adverse maternal outcomes including cesarean section (RR: 0.75, 95%CI: 0.63 to 0.89), maternal hospitalization (RR: 0.13, 95%CI: 0.02 to 0.98) and postpartum hemorrhage (RR: 0.47, 95%CI: 0.22 to 1.00). Several adverse neonatal complications including neonatal hyperbilirubinemia (RR: 0.47, 95%CI: 0.33 to 0.67), giant children (RR: 0.58, 95%CI: 0.38 to 0.89), polyhydramnios (RR: 0.42, 95% CI: 0.24 to 0.72), fetal distress (RR: 0.46, 95%CI: 0.24 to 0.90) and premature delivery (RR: 0.43, 95% CI: 0.26 to 0.72) were also significantly reduced. CONCLUSIONS: This meta-analysis suggested that supplementation of GDM women with vitamin D may lead to an improvement in glycemic control and reduction of adverse maternal-neonatal outcomes.

Influence of probiotic supplementation on the developing microbiota in human preterm neonates.

BACKGROUND: Oral administration of probiotic bacteria to preterm neonates has been recommended to prevent the development of necrotizing enterocolitis (NEC). The influence of probiotics on the endogenous microbiome, however, has remained incompletely understood. STUDY DESIGN & METHODS: Here, we performed an observational study including 80 preterm neonates born at a gestational age <32-weeks to characterize the persistence of probiotic bacteria after no treatment or oral administration of two different probiotic formula and their influence on the microbial ecosystem during and after the intervention and their association with the development of NEC. Weekly fecal samples were profiled by 16S rRNA sequencing and monitored for the presence of the probiotic bacteria by quantitative PCR. RESULTS: Microbiota profiles differed significantly between the control group and both probiotic groups. Probiotic supplementation was associated with lower temporal variation as well as higher relative abundance of Bifidobacterium and Enterobacter combined with reduced abundance of Escherichia, Enterococcus, and Klebsiella. Colonization by probiotic bifidobacteria was observed in approximately 50% of infants although it remained transient in the majority of cases. A significantly reduced monthly incidence of NEC was observed in neonates supplemented with probiotics. CONCLUSION: Our results demonstrate successful transient colonization by probiotic bacteria and a significant influence on the endogenous microbiota with a reduced abundance of bacterial taxa associated with the development of NEC. These results emphasize that probiotic supplementation may allow targeted manipulation of the enteric microbiota and confer a clinical benefit. (Clinical Trial Registry accession number: DRKS/GCTR 00021034).

Iodine status and supplementation before, during, and after pregnancy.

Iodine intake is essential for the production of thyroid hormone. Iodine deficiency remains a public health problem in many regions around the world. Iodine deficiency can present as a spectrum of disorders depending on the degree of severity. Pregnant and lactating women are particularly vulnerable to iodine deficiency disorders because of their increased iodine requirements. Severe maternal iodine deficiency has been associated with cretinism or impaired neurodevelopment in children as well as obstetric complications. Universal salt iodization has been shown to prevent these disorders in severely iodine deficient areas. Recently, observational studies have demonstrated an association between mild-to-moderate iodine deficiency and poorer cognitive outcomes in children. In this review, we describe the iodine requirements for pregnant and lactating women, how population iodine status can be assessed, the effects of maternal iodine deficiency and excess, and current data regarding efficacy of iodine supplementation for women who are pregnant or lactating.

Early Pregnancy Screening for Women at High-Risk of GDM Results in Reduced Neonatal Morbidity and Similar Maternal Outcomes to Routine Screening.

The Australasian Diabetes in Pregnancy Society recommends screening high-risk women for gestational diabetes mellitus (GDM) before 24 weeks gestation, under the assumption that an earlier diagnosis and opportunity to achieve normoglycemia will minimize adverse outcomes. However, little evidence exists for this recommendation. The study objective was to compare the pregnancy outcomes of high-risk women diagnosed with GDM before 24 weeks gestation and routinely diagnosed women after 24 weeks gestation. A retrospective audit was conducted of all pregnancies diagnosed with GDM using International Association of Diabetes and Pregnancy Study Groups criteria over 12 months at a tertiary Australian hospital. Adverse perinatal outcomes were compared between "Early GDM" diagnosed before 24 weeks (n = 133) and "Late GDM" diagnosed from 24 weeks (n = 636). Early GDM had a significantly lower newborn composite outcome frequency (hypoglycemia, birth trauma, NICU/SCN admission, stillbirth, neonatal death, respiratory distress, and phototherapy) compared to Late GDM (20.3% vs. 30.0%, p = 0.02). Primary cesarean, hypertensive disorders, postpartum hemorrhage, birthweight >90th percentile, macrosomia, and preterm birth frequencies were not significantly different between groups. Therefore, high-risk women diagnosed with GDM in early pregnancy were not more likely to have an adverse outcome compared to routinely diagnosed women. As they are a high-risk group, this may indicate a possible benefit to the early diagnosis of GDM.

'This sickness is not hospital sickness': a qualitative study of the evil eye as a source of neonatal illness in Ghana.

Previous research has described the evil eye as a source of illness for pregnant women and their newborns. This study sought to explore the perceptions of the evil eye among mothers whose newborns had experienced a life-threatening complication across three regions of Ghana. As part of a larger, quantitative study, trained research assistants identified pregnant and newly delivered women (and their newborns) who had survived a life-threatening complication at three tertiary care hospitals in southern Ghana to participate in open-ended, qualitative interviews about their experiences in March-August 2015. All interviews were audio-recorded and transcribed verbatim into English and analysis using the constant comparative method of theme generation. A total of 37 mothers were interviewed, 20 about neonatal illnesses and 17 about maternal illnesses. Six of the 20 mothers interviewed about their newborn's illnesses spoke at length about the evil eye being a potential cause of newborn illness. The evil eye was described in a variety of terms, but commonalities included a person looking at a pregnant woman, her newborn baby, the baby's clothes and even the mother's food, causing harm, even unintentionally. Prevention required mothers covering themselves while pregnant and keeping the baby away from others until it was old enough to ward off the evil eye. Treatment required traditional medicine, yet some indicated that allopathic medicine could help. The evil eye appears to serve a social control mechanism, encouraging pregnant women to dress modestly, stay indoors as much as possible and behave appropriately. The evil eye is a pervasive, universally understood phenomenon across three regions of Ghana, even amongst a hospitalized population receiving allopathic health care for life-threatening complications of childbirth. Understanding the role of the evil eye in newborn illness attribution is important for clinicians, researchers and programmatic staff to effectively address barriers to care seeking.

Docosahexaenoic acid supplementation of preterm infants and parent-reported symptoms of allergic disease at 7 years corrected age: follow-up of a randomized controlled trial.

BACKGROUND: Docosahexaenoic acid (DHA, 22:6n-3) supplementation in the prenatal period is associated with a reduction in the incidence of some symptoms of allergic disease. Infants born preterm are at increased risk of allergic disease, but it is unknown if DHA supplementation reduces the risk of childhood allergies. OBJECTIVES: The aim of this study was to determine if supplementation of infants born at <33 wk gestation with high-DHA compared with standard-DHA enteral feeds decreases the incidence and severity of parent-reported allergic disease symptoms at a corrected age (CA) of 7 y. METHODS: This study was a follow-up of an Australian multicenter randomized controlled trial. Infants were given high-DHA (∼1% total fatty acids) or standard-DHA (∼0.3% total fatty acids) enteral feeds from 2-4 d of postnatal age until 40 wk postmenstrual age. Parent-reported incidence of respiratory allergic disease symptoms including wheeze and rhinitis at 7 y CA were the main outcomes. Other outcomes included the incidence of eczema symptoms; severity of any symptoms; and the incidence of wheeze, rhinitis, rhinoconjunctivitis, and eczema from birth to 7 y CA. RESULTS: Data were available for 569 of 657 (87%) children originally randomized. Symptoms of wheeze or rhinitis at 7 y CA did not differ between high- and standard-DHA groups [wheeze: RR: 1.10; 95% CI: 0.73, 1.65; P = 0.66; rhinitis: RR: 1.09; 95% CI: 0.81, 1.46; P = 0.59]. There was no difference in other allergic disease symptoms at 7 y CA or in the severity of symptoms. Parent-reported symptoms of wheeze, rhinitis, rhinoconjunctivitis, or eczema from birth to 7 y CA did not differ between the groups. CONCLUSIONS: High-dose DHA supplementation of infants born at <33 wk gestation did not alter allergic disease symptoms or severity at 7 y CA, or from birth to 7 y CA compared with standard-dose DHA. This trial was registered with the Australian New Zealand Clinical Trials Registry as ANZCTR 12606000327583 (http://www.anzctr.org.au).

Influenza vaccination of pregnant women in Paris, France: Knowledge, attitudes and practices among midwives.

INTRODUCTION: In France, midwives have been authorized to prescribe vaccines since 2016. Yet vaccination coverage among pregnant women remains low. Understanding the knowledge, attitudes and practices of midwives regarding influenza vaccination could help improve coverage. METHODS: A cross-sectional survey was conducted in 2017 among midwives practicing in the public and private sectors in Paris using an online questionnaire. Multivariate logistic regression analysis of the data was conducted. RESULTS: The response rate was 31% (n = 208/669). Overall, knowledge of influenza vaccine recommendations and of vaccine safety and effectiveness was high except regarding new-born immunity and influenza vaccine characteristics. Only 10% of midwives systematically prescribed the vaccine. Reported influenza vaccine uptake among midwives was 39%. CONCLUSION: Efforts to improve the knowledge of midwives regarding the safety and effectiveness of vaccinating pregnant women in order to prevent influenza infection in newborns are necessary. Increasing vaccine uptake in both midwives and pregnant women will require adjusting education strategies.

Vitamin D Deficiency, Prevalence and Treatment in Neonatal Period.

OBJECTIVE: Maternal vitamin D deficiency is an important risk factor that causes infantile rickets in the neonatal and infantile period. The aim of this study was to review the prevalence, clinical characteristics, and treatment of vitamin D deficiency and the follow-ups with infants and their mothers by the neonatal intensive care unit of Afiyet Hospital in Turkey. METHODS: Calcium (Ca), phosphorus (P) and 25 (OH) vitamin D were studied and prospectively recorded in infants and their mothers detected to have hypocalcemia during routine biochemistry tests performed on the third postnatal day of the patients follow up and treated with different diagnoses. RESULTS: A total of 2,460 infants were admitted into the neonatal intensive care unit between August 2014 and January 2018. Of the infants included in the study, 324 (66.1%) were male and 166 (33.8%) were female, and 366 (74.6%) of them had been delivered by cesarean section (C/S), 124 (25.3%) of them had been delivered by Normal Spontaneous Delivery (NSD). Hypocalcemia was detected in 490 (19.9%) of the infants. In a total of 190 (38.7%) infants and 86 mothers (17.5%), the levels of 25 (OH) vitamin D were found to be below the laboratory detection limit of <3 ng/ml. When vitamin D deficiency + insufficiency is assessed by season, 151 of them were found to be in summer (30.99%), 118 in spring (24.18%), 117 in the winter season(23.87%), and 93 in autumn(18.97%), respectively. There was a statistically significant positive correlation of 78.7% between the vitamins D values of the mothers and the infants (p: 0.000, p<0.05). CONCLUSION: This study conducted that a positive correlation of between the vitamin D values of the mothers and the infants. In order to prevent maternal vitamin D deficiency, the appropriate dose of prophylaxis providing optimal levels of vitamin D and should be given by according to the levels of 25 (OH) D vitamin during pregnancy.

Efficacy of vitamin D supplementation in gestational diabetes mellitus: Systematic review and meta-analysis of randomized trials.

BACKGROUND: Trials have examined on the benefits of vitamin D supplementation in pregnant women. OBJECTIVE: This review aimed to evaluate whether oral vitamin D supplements, when given to pregnant women with gestational diabetes mellitus (GDM), would improve maternal and neonatal outcomes, compared with no treatment or placebo. METHOD: We performed a systematic review following Cochrane methodology, and randomized trials were included where pregnant women with GDM received vitamin D supplementation versus placebo/no treatment or vitamin D and calcium versus placebo/no treatment. Primary outcomes were preeclampsia, preterm birth, cesarean delivery, gestational hypertension, and adverse events related to vitamin D supplementation. The search strategies were applied to the following databases: MEDLINE, Embase, LILACS, and CENTRAL. Similar outcomes in at least two trials were plotted using Review Manager 5.3 software. The quality of evidence was generated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: The total of 1224 references were identified, eleven trials were potentially eligible, and six were included in this review (totaling 456 women). The meta-analysis of frequency of cesarean deliveries did not show significant differences between groups, none of the trials evaluated the remaining primary outcomes. For secondary outcomes, our results suggest that vitamin D supplementation in pregnant women with GDM may reduce newborn complications such as hyperbilirubinemia, polyhydramnios (RR: 0.40, 95% CI: 0.23 to 0.68; RR: 0.17, 95% CI: 0.03 to 0.89; respectively), and the need for maternal or infant hospitalization (RR: 0.13; 95% CI: 0.02 to 0.98; RR: 0.40, 95% CI: 0.23 to 0.69). However, the evidence was of low or very low quality. CONCLUSION: We did not find moderate or high quality evidence indicating that vitamin D supplementation, when compared with placebo, improves glucose metabolism, adverse maternal and neonatal outcomes related to GDM in pregnant women.

Can Postbiotics Represent a New Strategy for NEC?

Increasing evidence indicates that many of the health beneficial effects associated with the establishment of a symbiotic gut microbiota are driven by bacterial metabolic by-products.The term "postbiotics" indicates any soluble factor resulting from the metabolic activity of a live bacteria or any released molecule capable of providing health benefits through a direct or indirect mechanism.Alterations in preterm gut colonization associated with the intestinal barrier immaturity and the increased reactivity of the intestinal mucosa to colonizing bacteria have been implicated in the pathogenesis of necrotizing enterocolitis. Recent advances in the comprehension of the postbiotic biological effects and related mechanisms, some of them reviewed here, indicate that postbiotics may be a promising effective preventive strategy against necrotizing enterocolitis while avoiding the risk of administering live microorganisms to preterm infants that could translocate and cause infection. However, data from trials investigating the efficacy of postbiotics for the prevention of necrotizing enterocolitis in preterm infants are needed, and issues regarding their optimal regimen and start and duration of treatment need to be addressed.

"We shall count it as a part of kyogero": acceptability and considerations for scale up of single dose chlorhexidine for umbilical cord care in Central Uganda.

BACKGROUND: Cleansing the umbilical cord with chlorhexidine reduces neonatal morbidity and mortality, particularly in communities where newborn deaths and home births are common. As a result, the World Health Organization and national authorities are advocating the scale up of this intervention. In order for such a scale up to be effective, it has to be acceptable to the targeted population. With the overall aim to clarify conditions for scale-up, this study explored the acceptability of single dose chlorhexidine solution for umbilical cord care among health workers and infant care providers in the districts of Kampala and Mukono in Central Uganda. METHODS: This was a qualitative study that involved mothers of neonates enrolled in a chlorhexidine trial, nurses implementing the trial, key community members and opinion leaders in childcare. We conducted 30 in depth interviews (IDIs) with mothers (18), health workers (8), traditional birth attendants (2), a father (1) and a grandmother (1) and 4 focus group discussions (FGDs), 3 with mothers and 1 with health workers. We used qualitative content analysis to analyze our findings and borrow upon Sekhon's model when presenting our findings. RESULTS: Cognitive and emotional responses to chlorhexidine use included ease of use, and a perception that chlorhexidine reduced smell and abdominal colic. We also found that wider social and cultural factors were important to chlorhexidine use. These included cultural value put on quick separation of the umbilical cord as well as the practice of bathing the baby in a herbal mixture called kyogero. We also found that older relatives were key decision makers in umbilical cord care for newborns, but were seldom present during health workers' counseling of mothers about hygienic care of the cord. CONCLUSIONS: The application of chlorhexidine on the umbilical cord stump at birth was acceptable as an addition rather than a total replacement of traditional substances. The scale up of chlorhexidine should consider how to accommodate local beliefs and practices in a way that does not compromise the effect of the intervention; encouraging mothers to delay the bathing of babies in kyogero could be one way of doing this.

Lactoferrin: A Critical Player in Neonatal Host Defense.

Newborn infants are at a high risk for infection due to an under-developed immune system, and human milk has been shown to exhibit substantial anti-infective properties that serve to bolster neonatal defenses against multiple infections. Lactoferrin is the dominant whey protein in human milk and has been demonstrated to perform a wide array of antimicrobial and immunomodulatory functions and play a critical role in protecting the newborn infant from infection. This review summarizes data describing the structure and important functions performed by lactoferrin in protecting the neonate from infection and contributing to the maturation of the newborn innate and adaptive immune systems. We also briefly discuss clinical trials examining the utility of lactoferrin supplementation in the prevention of sepsis and necrotizing enterocolitis in newborn infants. The data reviewed provide rationale for the continuation of studies to examine the effects of lactoferrin administration on the prevention of sepsis in the neonate.

The effects of enteral feeding improvement massage on premature infants: A randomised controlled trial.

AIMS AND OBJECTIVES: To prove the effects of an enteral feeding improvement massage for premature infants with regard to their feeding, growing and superior mesentery artery blood flow aspect by a randomised controlled trial. BACKGROUND: Premature infants have feeding-related problems related to eating and absorbing nutrition due to their immature gastrointestinal function. Studies regarding the effectiveness of premature infants' enteral feeding improvement by tactile stimulation massage are rare. DESIGN: The study group was composed of 55 patients. Of the 55 patients, 26 were randomised into an experimental group and 29 were randomised into a control group. METHODS: They were all born <34 weeks of gestational age between 1 July 2011 and 30 March 2012. Premature infants in the experimental group received enteral feeding improvement massage twice a day for 14 days, and infants in the control group received a sham exercise. The collected data were analysed by spss 19.0, through t test, chi-square test (Fisher's exact) and ANCOVA. RESULTS: (i) The experimental group had reached the day of full enteral feeding significantly faster. (ii) The experimental group had a higher superior mesentery artery peak velocity (Vmax ) and lower RI (resistant index). (iii) The experimental group of the feeding-intolerant subgroup had a higher superior mesentery artery Vmax and Vmin . (iv) The experimental group had a heavier weight and larger head circumference after 14 days. CONCLUSIONS: This study demonstrates that enteral feeding improvement massage can be helpful for achieving earlier full enteral feeding, more increased superior mesentery artery, and faster growing. In particular, it can be a therapeutic, independent and evidence-based nursing intervention for feeding-intolerant premature infants. RELEVANCE TO CLINICAL PRACTICE: Neonatal nurses in neonatal intensive care unit can apply enteral feeding improvement massage massage for feeding-intolerant infants.

Prenatal early food and multiple micronutrient supplementation trial reduced infant mortality in Bangladesh, but did not influence morbidity.

AIM: A previous maternal and infant nutrition intervention in rural Matlab, Bangladesh, showed that prenatal nutrient supplements improved child survival, but had no effect on size at birth. This secondary analysis examined whether prenatal multiple micronutrient supplements (MMS), on their own or combined with an early invitation to receive prenatal food supplements, affected child morbidity. METHODS: This randomised trial enrolled 4436 pregnant women from November 2001 to October 2003 and allocated them to early or standard invitations to food supplements, in the ninth and 20th weeks of pregnancy, respectively, and supplements of either the standard 60 mg iron with 400 µg folic acid, 30 mg iron with 400 µg folic acid or MMS. Quasi-Poisson regression was used to analyse morbidity. RESULTS: There were 3560 single live births and 3516 had morbidity data. The incidence rates of fever, diarrhoea and acute lower respiratory tract infection were 15.3, 3.6 and 2.3 episodes per person-year, respectively. The separate or combined interventions had no effect on morbidity up to 24 months. CONCLUSION: Early invitations to prenatal food supplements or prenatal MMS had no effect on common infections in rural Bangladesh, suggesting that earlier findings on improved child survival were not mediated by an effect on child morbidity.

Vitamin C Prevents Offspring DNA Methylation Changes Associated with Maternal Smoking in Pregnancy.

RATIONALE: Infants whose mothers smoked during pregnancy demonstrate lifelong decreases in pulmonary function. DNA methylation changes associated with maternal smoking during pregnancy have been described in placenta and cord blood at delivery, in fetal lung, and in buccal epithelium and blood during childhood. We demonstrated in a randomized clinical trial ( ClinicalTrials.gov identifier, NCT00632476) that vitamin C supplementation to pregnant smokers can lessen the impact of maternal smoking on offspring pulmonary function and decrease the incidence of wheeze at 1 year of age. OBJECTIVES: To determine whether vitamin C supplementation reduces changes in offspring methylation in response to maternal smoking and whether methylation at specific CpGs is also associated with respiratory outcomes. METHODS: Targeted bisulfite sequencing was performed with a subset of placentas, cord blood samples, and buccal samples collected during the NCT00632476 trial followed by independent validation of selected cord blood differentially methylated regions, using bisulfite amplicon sequencing. MEASUREMENTS AND MAIN RESULTS: The majority (69.03%) of CpGs with at least 10% methylation difference between placebo and nonsmoker groups were restored (by at least 50%) toward nonsmoker levels with vitamin C treatment. A significant proportion of restored CpGs were associated with phenotypic outcome with greater enrichment among hypomethylated CpGs. CONCLUSIONS: We identified a pattern of normalization in DNA methylation by vitamin C supplementation across multiple loci. The consistency of this pattern across tissues and time suggests a systemic and persistent effect on offspring DNA methylation. Further work is necessary to determine how genome-wide changes in DNA methylation may mediate or reflect persistent effects of maternal smoking on lung function.

Vitamin D administration during pregnancy as prevention for pregnancy, neonatal and postnatal complications.

Pregnancy represents a time of rapid bodily change, which includes physical proportions, physiology and responsibility. At this context, maternal vitamin D stores have been the objective of extensive scientific research during the last decades, focusing on their potential effects on maternal an neonatal health. A growing body of observational studies indicated that maternal hypovitaminosis D (as defined by maternal 25-hydroxyvitamin D [25(OH)D] levels <20 ng/ml or <50 nmol/l) is a significant risk factor for adverse neonatal outcomes including asthma, multiple sclerosis and other neurological disorders. On that basis, this review aims to provide to the reader new insights into the vitamin D requirements and function during pregnancy supported by recent data and will not discuss the classical roles of vitamin D and skeletal function during pregnancy. In addition, we will focus on recent results that demonstrate that maternal vitamin D supplementation could reduce neonatal respiratory and neurological complications, suggesting that available guidelines should be updated, since it remains unclear why these recommendations are not updated according to recent results. Also, with regard to randomized controlled trials (RCT's) for vitamin D, we consider that they are largely doomed to fail. The reasons for this are many and specific cases of this failure will be presented in this text.

Maternal vitamin D supplementation during pregnancy and lactation to prevent acute respiratory infections in infancy in Dhaka, Bangladesh (MDARI trial): protocol for a prospective cohort study nested within a randomized controlled trial.

BACKGROUND: Early infancy is a high-risk period for severe acute respiratory infection (ARI), particularly in low-income countries with resource-limited health systems. Lower respiratory tract infection (LRTI) is commonly preceded by upper respiratory infection (URTI), and often caused by respiratory syncytial virus (RSV), influenza and other common community-acquired viral pathogens. Vitamin D status is a candidate modifiable early-life determinant of the host antiviral immune response and thus may influence the risk of ARI-associated morbidity in high-risk populations. METHODS/DESIGN: In the Maternal Vitamin D for Infant Growth (MDIG) study in Dhaka, Bangladesh (NCT01924013), 1300 pregnant women are randomized to one of five groups: placebo, 4200 IU/week, 16,800 IU/week, or 28,000 IU/week from 2nd trimester to delivery plus placebo from 0-6 months postpartum; or, 28,000 IU/week prenatal and until 6-months postpartum. In the Maternal Vitamin D for ARI in Infancy (MDARI) sub-study nested within the MDIG trial, trained personnel conduct weekly postnatal home visits to inquire about ARI symptoms and conduct a standardized clinical assessment. Supplementary home visits between surveillance visits are conducted when caregivers make phone notifications of new infant symptoms. Mid-turbinate nasal swab samples are obtained from infants who meet standardized clinical ARI criteria. Specimens are tested by polymerase chain reaction (PCR) for 8 viruses (influenza A/B, parainfluenza 1/2/3, RSV, adenovirus, and human metapneumovirus), and nasal carriage density of Streptococcus pneumoniae. The primary outcome is the incidence rate of microbiologically-positive viral ARI, using incidence rate ratios to estimate between-group differences. We hypothesize that among infants 0-6 months of age, the incidence of microbiologically-confirmed viral ARI will be significantly lower in infants whose mothers received high-dose prenatal/postpartum vitamin D supplements versus placebo. Secondary outcomes include incidence of ARI associated with specific pathogens (influenza A or B, RSV), clinical ARI, and density of pneumococcal carriage. DISCUSSION: If shown to reduce the risk of viral ARI in infancy, integration of maternal prenatal/postpartum vitamin D supplementation into antenatal care programs in South Asia may be a feasible primary preventive strategy to reduce the burden of ARI-associated morbidity and mortality in young infants. TRIAL REGISTRATION: NCT02388516 , registered March 9, 2015.

Nifedipine maintenance tocolysis and perinatal outcome: an individual participant data meta-analysis.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality and morbidity in developed countries. Whether continued tocolysis after 48 hours of rescue tocolysis improves neonatal outcome is unproven. OBJECTIVES: To evaluate the effectiveness of maintenance tocolytic therapy with oral nifedipine on the reduction of adverse neonatal outcomes and the prolongation of pregnancy by performing an individual patient data meta-analysis (IPDMA). SEARCH STRATEGY: We searched PubMed, Embase, and Cochrane databases for randomised controlled trials of maintenance tocolysis therapy with nifedipine in preterm labour. SELECTION CRITERIA: We selected trials including pregnant women between 24 and 36(6/7)  weeks of gestation (gestational age, GA) with imminent preterm labour who had not delivered after 48 hours of initial tocolysis, and compared maintenance nifedipine tocolysis with placebo/no treatment. DATA COLLECTION AND ANALYSIS: The primary outcome was perinatal mortality. Secondary outcome measures were intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), infant respiratory distress syndrome (IRDS), prolongation of pregnancy, GA at delivery, birthweight, neonatal intensive care unit admission, and number of days on ventilation support. Pre-specified subgroup analyses were performed. MAIN RESULTS: Six randomised controlled trials were included in this IPDMA, encompassing data from 787 patients (n = 390 for nifedipine; n = 397 for placebo/no treatment). There was no difference between the groups for the incidence of perinatal death (risk ratio, RR 1.36; 95% confidence interval, 95% CI 0.35-5.33), intraventricular haemorrhage (IVH) ≥ grade II (RR 0.65; 95% CI 0.16-2.67), necrotising enterocolitis (NEC) (RR 1.15; 95% CI 0.50-2.65), infant respiratory distress syndrome (IRDS) (RR 0.98; 95% CI 0.51-1.85), and prolongation of pregnancy (hazard ratio, HR 0.74; 95% CI 0.55-1.01). CONCLUSION: Maintenance tocolysis is not associated with improved perinatal outcome and is therefore not recommended for routine practice. TWEETABLE ABSTRACT: Nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation.