Sponsors asked the IOM's Food and Nutrition Board and the Division of Behavioral and Social Sciences and Education Board on Children, Youth, and Families to review and update the IOM (1990) recommendations for weight gain during pregnancy and recommend ways to encourage their adoption through consumer education, strategies to assist practitioners, and public health strategies.The committee was asked to address the following tasks: 1. Review evidence on the relationship between weight gain patterns before, during, and after pregnancy and maternal and child health outcomes, with particular attention to the prevalence of maternal obesity racial/ethnic and age differences, components of GWG, and implications of weight during pregnancy on postpartum weight retention, maternal and child obesity, and later child health. 2. Within a life-stage framework consider factors in relation to GWG that are associated with maternal health outcomes such as lactation performance, postpartum weight retention, cardiovascular disease, metabolic processes including glucose and insulin-related issues, and risk of other chronic diseases; for infants and children, in addition to low birth weight, consider early developmental impacts and obesity-related consequences (e.g., mental health, diabetes). 3. Recommend revisions to the existing guidelines, where necessary, including the need for specific pregnancy weight guidelines for underweight, normal weight, and overweight and obese women and adolescents and women carrying twins or higher-order multiples. 4. Consider a range of approaches to promote appropriate weight gain, including: individual (behavior), psychosocial, community, health care, and health systems; timing and components of interventions; and ways to enhance awareness and adoption of the guidelines, including interdisciplinary approaches, consumer education to men and women, strategies to assist practitioners to use the guidelines, and public health strategies. 5. Identify gaps in knowledge and recommend research priorities.

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Weight Gain During Pregnancy: Reexamining the Guidelines

The aim of this study was to revise the 2003 Fenton Preterm Growth Chart, specifically to: a) harmonize the preterm growth chart with the new World Health Organization (WHO) Growth Standard, b) smooth the data between the preterm and WHO estimates, informed by the Preterm Multicentre Growth (PreM Growth) study while maintaining data integrity from 22 to 36 and at 50 weeks, and to c) re-scale the chart x-axis to actual age (rather than completed weeks) to support growth monitoring. Systematic review, meta-analysis, and growth chart development. We systematically searched published and unpublished literature to find population-based preterm size at birth measurement (weight, length, and/or head circumference) references, from developed countries with: Corrected gestational ages through infant assessment and/or statistical correction; Data percentiles as low as 24 weeks gestational age or lower; Sample with greater than 500 infants less than 30 weeks. Growth curves for males and females were produced using cubic splines to 50 weeks post menstrual age. LMS parameters (skew, median, and standard deviation) were calculated. Six large population-based surveys of size at preterm birth representing 3,986,456 births (34,639 births < 30 weeks) from countries Germany, United States, Italy, Australia, Scotland, and Canada were combined in meta-analyses. Smooth growth chart curves were developed, while ensuring close agreement with the data between 24 and 36 weeks and at 50 weeks. The revised sex-specific actual-age growth charts are based on the recommended growth goal for preterm infants, the fetus, followed by the term infant. These preterm growth charts, with the disjunction between these datasets smoothing informed by the international PreM Growth study, may support an improved transition of preterm infant growth monitoring to the WHO growth charts.

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A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants

Objective  To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design  Systematic review and meta-analysis of cohort studies. Data sources  PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies  Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction  Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results  There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions  There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

https://www.bmj.com/content/bmj/353/bmj.i1753.full.pdf

Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

Background
Multiple-micronutrient (MMN) deficiencies often coexist among women of reproductive age in low- to middle-income countries. They are exacerbated in pregnancy due to the increased demands, leading to potentially adverse effects on the mother and developing fetus. Though supplementation with MMNs has been recommended earlier because of the evidence of impact on pregnancy outcomes, a consensus is yet to be reached regarding the replacement of iron and folic acid supplementation with MMNs. Since the last update of this Cochrane review, evidence from a few large trials has recently been made available, the inclusion of which is critical to inform policy.

Objectives
To evaluate the benefits of oral multiple-micronutrient supplementation during pregnancy on maternal, fetal and infant health outcomes.

Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (11 March 2015) and reference lists of retrieved articles and key reviews. We also contacted experts in the field for additional and ongoing trials.

Selection criteria
All prospective randomised controlled trials evaluating MMN supplementation with iron and folic acid during pregnancy and its effects on the pregnancy outcome were eligible, irrespective of language or the publication status of the trials. We included cluster-randomised trials, but quasi-randomised trials were excluded.

Data collection and analysis
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach.

Main results
Nineteen trials (involving 138,538 women) were identified as eligible for inclusion in this review but only 17 trials (involving 137,791 women) contributed data to the review. Fifteen of these 17 trials were carried out in low and middle-income countries and compared MMN supplements with iron and folic acid versus iron with or without folic acid. Two trials carried out in the UK compared MMN with a placebo.

MMN with iron and folic acid versus iron, with or without folic acid (15 trials): MMN resulted in a significant decrease in the number of newborn infants identified as low birthweight (LBW) (average risk ratio (RR) 0.88, 95% confidence interval (CI) 0.85 to 0.91; high-quality evidence) or small-for-gestational age (SGA) (average RR 0.92, 95% CI 0.86 to 0.98; moderate-quality evidence). No significant differences were shown for other maternal and pregnancy outcomes: preterm births (average RR 0.96, 95% CI 0.90 to 1.03; high-quality evidence), stillbirth (average RR 0.97, 95% CI 0.87, 1.09; high-quality evidence), maternal anaemia in the third trimester (average RR 1.03, 95% CI 0.85 to 1.24), miscarriage (average RR 0.91, 95% CI 0.80 to 1.03), maternal mortality (average RR 0.97, 95% CI 0.63 to 1.48), perinatal mortality (average RR 1.01, 95% CI 0.91 to 1.13; high-quality evidence), neonatal mortality (average RR 1.06, 95% CI 0.92 to 1.22; high-quality evidence), or risk of delivery via a caesarean section (average RR 1.04; 95% CI 0.74 to 1.46).

A number of prespecified, clinically important outcomes could not be assessed due to insufficient or non-available data. Single trials reported results for: very preterm birth < 34 weeks, macrosomia, side-effects of supplements, nutritional status of children, and congenital anomalies including neural tube defects and neurodevelopmental outcome: Bayley Scales of Infant Development (BSID) scores. None of these trials reported pre-eclampsia, placental abruption, premature rupture of membranes, cost of supplementation, and maternal well-being or satisfaction.

When assessed according to GRADE criteria, the quality of evidence for the review's primary outcomes overall was good. Pooled results for primary outcomes were based on multiple trials with large sample sizes and precise estimates. The following outcomes were graded to be as of high quality: preterm birth, LBW, perinatal mortality, stillbirth and neonatal mortality. The outcome of SGA was graded to be of moderate quality, with evidence downgraded by one for funnel plot asymmetry and potential publication bias.

We carried out sensitivity analysis excluding trials with high levels of sample attrition (> 20%); results were consistent with the main analysis except for the findings for SGA (average RR 0.91, 95% CI 0.84 to 1.00). We explored heterogeneity through subgroup analyses by maternal height and body mass index (BMI), timing of supplementation and dose of iron. Subgroup differences were observed for maternal BMI for the outcome preterm birth, with significant findings among women with low BMI. Subgroup differences were also observed for maternal BMI and maternal height for the outcome SGA, indicating a significant impact among women with higher maternal BMI and height. The overall analysis of perinatal mortality, although showed a non-significant effect of MMN supplements versus iron with or without folic acid, was found to have substantial statistical heterogeneity. Subgroup differences were observed for timing of supplementation for this outcome, indicating a significantly higher impact with late initiation of supplementation. The findings between subgroups for other primary outcomes were inconclusive.

MMN versus placebo (two trials): A single trial in the UK found no clear differences between groups for preterm birth, SGA, LBW or maternal anaemia in the third trimester. A second trial reported the number of women with pre-eclampsia; there was no evidence of a difference between groups. Other outcomes were not reported.

Authors' conclusions
Our findings support the effect of MMN supplements with iron and folic acid in improving some birth outcomes. Overall, pregnant women who received MMN supplementation had fewer low birthweight babies and small-for-gestational-age babies. The findings, consistently observed in several systematic evaluations of evidence, provide a basis to guide the replacement of iron and folic acid with MMN supplements containing iron and folic acid for pregnant women in low and middle-income countries where MMN deficiencies are common among women of reproductive age. Efforts could focus on the integration of this intervention in maternal nutrition and antenatal care programs in low and middle-income countries.

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Multiple‐micronutrient supplementation for women during pregnancy

WHAT'S KNOWN ON THIS SUBJECT: Colic affects many infants, with incidence rates of up to 25%. The pathogenesis is not well understood. Initial studies based on traditional culturing approaches and in infants .6 weeks of age point at abnormalities in intestinal microbiota. WHAT THIS STUDY ADDS: Infants with colic showed lower microbiota diversity and stability than did control infants in the first weeks of life. Colic/control differences in the abundance of certain bacteria were also found at age 2 weeks. These microbial signatures possibly explain the excessive crying. abstract To provide a comprehensive analysis of the fecal micro- biota in infants with colic, as compared with control infants, during their first 100 days of life. METHODS: Microbial DNA of .200 samples from 12 infants with colic and 12 age-matched control infants was extracted and hybridized to a phylogenetic microarray. RESULTS: Microbiota diversity gradually increased after birth only in the control group; moreover, in the first weeks, the diversity of the colic group was significantly lower than that of the control group. The sta- bility of the successive samples also appeared to be significantly lower in the infants with colic for the first weeks. Further analyses revealed which bacterial groups were responsible for colic-related differences in microbiota at age 1 or 2 weeks, the earliest ages with significant differences. Proteobacteria were significantly increased in infants with colic compared with control infants, with a relative abundance that was more than twofold. In contrast, bifidobacteria and lactobacilli were significantly reduced in infants with colic. Moreover, the colic phenotype correlated positively with specifi cg roups of proteobacteria, including bacteria related to Escherichia, Klebsiella, Serratia, Vibrio, Yersinia, and Pseudomonas, but negatively with bacteria belonging to the Bacteroidetes and Firmicutes phyla, the latter of which includes some lactobacilli and canonical groups known to produce butyrate and lactate. CONCLUSIONS: The results indicate the presence of microbial signa- tures in the first weeks of life in infants who later develop colic. These microbial signatures may be used to understand the excessive crying. The results offer opportunities for early diagnostics as well as for developing specific therapies. Pediatrics 2013;131:e550-e558

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Intestinal Microbiota of Infants With Colic: Development and Specific Signatures

In perinatal medicine, severe obesity of the mother occurs in approximately 1% of cases. This is a problem of increasing importance because of the rising prevalence of juvenile obesity. Our retrospective cohort study aimed at characterising high-risk pregnancies associated with morbid obesity (body mass index [BMI]> or =40). This is of interest not only from an epidemiological perspective and for developing guidelines for clinical care but also from an anthropological point of view. We analysed the German perinatal statistics of the years 1998-2000 with data from more than 500,000 pregnancies. Pregnant women with coexistent morbid obesity were compared to a normal weight reference sample with regard to gestational, perinatal and neonatal risks. Birth weight percentiles were used to classify the neonates according to size (hypotrophy if 90th). The obtained risk profile for morbidly obese pregnant women primarily showed pregnancy related diseases, such as hypertension, pre-eclampsia and gestational diabetes. Hypertension and signs of foetal hypoxaemia occurred at higher frequencies with morbid obesity. Hypertrophic neonates were born 3.3 times more often to obese mothers than to mothers of the normal weight. At a BMI> or =40 the rates of complications such as pre-eclampsia, gestational diabetes, impending foetal hypoxaemia, foetal macrosomia, as well as neonatal infections and hyperbilirubinaemia were significantly higher. Obesity and maternal comorbidities, accounted for a higher rate of caesarean sections of up to 38.4% at a BMI> or =45. All differences were highly significant. Preconceptionally, the therapeutic approach should be weight reduction.

Morbid obesity: pregnancy risks, birth risks and status of the newborn.

Purpose
To compare risks of pregnancy and birth in obese (body mass index, BMI ≥ 30) and normal weight women (BMI 18.5–24.99) giving birth to their first child.

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Risks of pregnancy and birth in obese primiparous women: an analysis of German perinatal statistics.

Using data from a sample of German women, this paper analyzes the relationship between maternal characteristics and infants' birth weight and pre-term delivery. Besides typical epidemiological factors that influence the weight of infants, such as the gestational age and maternal BMI at the beginning of the pregnancy, we find a West--East gradient. Within West Germany, there is a small North-South gradient in birth weight, with larger birth weights in the north. Better educated mothers give birth to heavier babies and have a somewhat decreased risk of pre-term delivery. Income plays a minor role, while occupational status is not associated with the weight of infants at all.

The relationship between maternal characteristics, birth weight and pre-term delivery: evidence from Germany at the end of the 20th century.

OBJECTIVE Birth weight percentiles based on weekly measurements are used to assess the nutritional status of preterm infants. However, as preterm infants exhibit a rapid growth rate (up to 20 g/kg/day), their body weight can increase by 15% per week. We calculated birth weight percentiles based on daily measurements, to more precisely classify very preterm infants (gestational age of 154-223 days). METHODS Data of 23,864 (10,720 females and 13,144 males) very preterm singleton infants with a gestational age of 154-223 days (22-31 completed weeks) were retrieved from the German perinatal statistics of 1995-2000. Percentile curves based on the empirical birth weight data were subjected to three statistical smoothing procedures: cubic regression, local regression (LOESS smoothing), and the LMS method. RESULTS Smoothing of the birth weight percentiles using cubic regression produced the smallest residual variance. CONCLUSION Birth weight percentiles based on daily averages allow a more precise assessment of the somatic development of preterm infants.

Manfred Voigt

Papers

Morbid obesity: pregnancy risks, birth risks and status of the newborn.

Risks of pregnancy and birth in obese primiparous women: an analysis of German perinatal statistics.

The relationship between maternal characteristics, birth weight and pre-term delivery: evidence from Germany at the end of the 20th century.

Birth weight percentile charts based on daily measurements for very preterm male and female infants at the age of 154-223 days.

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