Mariangela Freitas da Silveira

The associations of parity and maternal age with small-for-gestational-age preterm and neonatal and infant mortality: a meta-analysis.

BackgroundPrevious studies have reported on adverse neonatal outcomes associated with parity and maternal age. Many of these studies have relied on cross-sectional data, from which drawing causal inference is complex. We explore the associations between parity/maternal age and adverse neonatal outcomes using data from cohort studies conducted in low- and middle-income countries (LMIC).MethodsData from 14 cohort studies were included. Parity (nulliparous, parity 1-2, parity ≥3) and maternal age (<18 years, 18-<35 years, ≥35 years) categories were matched with each other to create exposure categories, with those who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small-for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds ratios (aOR) were calculated per study and meta-analyzed.ResultsNulliparous, age <18 year women, compared with women who were parity 1-2 and age 18-<35 years had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR: 1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR: 1.49). Increased odds were also noted for SGA and neonatal mortality for nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity ≥3/age 18-<35 years, and preterm and neonatal mortality for parity ≥3/≥35 years.ConclusionsNulliparous women <18 years of age have the highest odds of adverse neonatal outcomes. Family planning has traditionally been the least successful in addressing young age as a risk factor; a renewed focus must be placed on finding effective interventions that delay age at first birth. Higher odds of adverse outcomes are also seen among parity ≥3 / age ≥35 mothers, suggesting that reproductive health interventions need to address the entirety of a woman’s reproductive period.FundingFunding was provided by the Bill & Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group.

Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis

BACKGROUND Babies with low birthweight (<2500 g) are at increased risk of early mortality. However, low birthweight includes babies born preterm and with fetal growth restriction, and not all these infants have a birthweight less than 2500 g. We estimated the neonatal and infant mortality associated with these two characteristics in low-income and middle-income countries. METHODS For this pooled analysis, we searched all available studies and identified 20 cohorts (providing data for 2,015,019 livebirths) from Asia, Africa, and Latin America that recorded data for birthweight, gestational age, and vital statistics through 28 days of life. Study dates ranged from 1982 through to 2010. We calculated relative risks (RR) and risk differences (RD) for mortality associated with preterm birth (<32 weeks, 32 weeks to <34 weeks, 34 weeks to <37 weeks), small-for-gestational-age (SGA; babies with birthweight in the lowest third percentile and between the third and tenth percentile of a US reference population), and preterm and SGA combinations. FINDINGS Pooled overall RRs for preterm were 6·82 (95% CI 3·56-13·07) for neonatal mortality and 2·50 (1·48-4·22) for post-neonatal mortality. Pooled RRs for babies who were SGA (with birthweight in the lowest tenth percentile of the reference population) were 1·83 (95% CI 1·34-2·50) for neonatal mortality and 1·90 (1·32-2·73) for post-neonatal mortality. The neonatal mortality risk of babies who were both preterm and SGA was higher than that of babies with either characteristic alone (15·42; 9·11-26·12). INTERPRETATION Many babies in low-income and middle-income countries are SGA. Preterm birth affects a smaller number of neonates than does SGA, but is associated with a higher mortality risk. The mortality risks associated with both characteristics extend beyond the neonatal period. Differentiation of the burden and risk of babies born preterm and SGA rather than with low birthweight could guide prevention and management strategies to speed progress towards Millennium Development Goal 4--the reduction of child mortality. FUNDING Bill & Melinda Gates Foundation.

National and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010

Summary Background National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (<2500 g), in 138 countries of low and middle income in 2010. Methods Small for gestational age was defined as lower than the 10th centile for fetal growth from the 1991 US national reference population. Data from 22 birth cohort studies (14 low-income and middle-income countries) and from the WHO Global Survey on Maternal and Perinatal Health (23 countries) were used to model the prevalence of term-SGA births. Prevalence of preterm-SGA infants was calculated from meta-analyses. Findings In 2010, an estimated 32·4 million infants were born small for gestational age in low-income and middle-income countries (27% of livebirths), of whom 10·6 million infants were born at term and low birthweight. The prevalence of term-SGA babies ranged from 5·3% of livebirths in east Asia to 41·5% in south Asia, and the prevalence of preterm-SGA infants ranged from 1·2% in north Africa to 3·0% in southeast Asia. Of 18 million low-birthweight babies, 59% were term-SGA and 41% were preterm. Two-thirds of small-for-gestational-age infants were born in Asia (17·4 million in south Asia). Preterm-SGA babies totalled 2·8 million births in low-income and middle-income countries. Most small-for-gestational-age infants were born in India, Pakistan, Nigeria, and Bangladesh. Interpretation The burden of small-for-gestational-age births is very high in countries of low and middle income and is concentrated in south Asia. Implementation of effective interventions for babies born too small or too soon is an urgent priority to increase survival and reduce disability, stunting, and non-communicable diseases. Funding Bill & Melinda Gates Foundation by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group (CHERG).

The associations of birth intervals with small-for-gestational-age, preterm, and neonatal and infant mortality: a meta-analysis

BackgroundShort and long birth intervals have previously been linked to adverse neonatal outcomes. However, much of the existing literature uses cross-sectional studies, from which deriving causal inference is complex. We examine the association between short/long birth intervals and adverse neonatal outcomes by calculating and meta-analyzing associations using original data from cohort studies conducted in low-and middle-income countries (LMIC).MethodsWe identified five cohort studies. Adjusted odds ratios (aOR) were calculated for each study, with birth interval as the exposure and small-for-gestational-age (SGA) and/or preterm birth, and neonatal and infant mortality as outcomes. The associations were controlled for potential confounders and meta-analyzed.ResultsBirth interval of shorter than 18 months had statistically significant increased odds of SGA (pooled aOR: 1.51, 95% CI: 1.31-1.75), preterm (pooled aOR: 1.58, 95% CI: 1.19-2.10) and infant mortality (pooled aOR: 1.83, 95% CI: 1.19-2.81) after controlling for potential confounding factors (reference 36-<60 months). It was also significantly associated with term-SGA, preterm-appropriate-for-gestational-age, and preterm-SGA. Birth interval over 60 months had increased risk of SGA (pooled aOR: 1.22, 95% CI: 1.07-1.39) and term-SGA (pooled aOR: 1.14, 95% CI: 1.03-1.27), but was not associated with other outcomes.ConclusionsBirth intervals shorter than 18 months are significantly associated with SGA, preterm birth and death in the first year of life. Lack of access to family planning interventions thus contributes to the burden of adverse birth outcomes and infant mortality in LMICs. Programs and policies must assess ways to provide equitable access to reproductive health interventions to mothers before or soon after delivering a child, but also address underlying socioeconomic factors that may modify and worsen the effect of short intervals.

Short Maternal Stature Increases Risk of Small-for-Gestational-Age and Preterm Births in Low- and Middle-Income Countries: Individual Participant Data Meta-Analysis and Population Attributable Fraction

BACKGROUND Small-for-gestational-age (SGA) and preterm births are associated with adverse health consequences, including neonatal and infant mortality, childhood undernutrition, and adulthood chronic disease. OBJECTIVES The specific aims of this study were to estimate the association between short maternal stature and outcomes of SGA alone, preterm birth alone, or both, and to calculate the population attributable fraction of SGA and preterm birth associated with short maternal stature. METHODS We conducted an individual participant data meta-analysis with the use of data sets from 12 population-based cohort studies and the WHO Global Survey on Maternal and Perinatal Health (13 of 24 available data sets used) from low- and middle-income countries (LMIC). We included those with weight taken within 72 h of birth, gestational age, and maternal height data (n = 177,000). For each of these studies, we individually calculated RRs between height exposure categories of < 145 cm, 145 to < 150 cm, and 150 to < 155 cm (reference: ≥ 155 cm) and outcomes of SGA, preterm birth, and their combination categories. SGA was defined with the use of both the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) birth weight standard and the 1991 US birth weight reference. The associations were then meta-analyzed. RESULTS All short stature categories were statistically significantly associated with term SGA, preterm appropriate-for-gestational-age (AGA), and preterm SGA births (reference: term AGA). When using the INTERGROWTH-21st standard to define SGA, women < 145 cm had the highest adjusted risk ratios (aRRs) (term SGA-aRR: 2.03; 95% CI: 1.76, 2.35; preterm AGA-aRR: 1.45; 95% CI: 1.26, 1.66; preterm SGA-aRR: 2.13; 95% CI: 1.42, 3.21). Similar associations were seen for SGA defined by the US reference. Annually, 5.5 million term SGA (18.6% of the global total), 550,800 preterm AGA (5.0% of the global total), and 458,000 preterm SGA (16.5% of the global total) births may be associated with maternal short stature. CONCLUSIONS Approximately 6.5 million SGA and/or preterm births in LMIC may be associated with short maternal stature annually. A reduction in this burden requires primary prevention of SGA, improvement in postnatal growth through early childhood, and possibly further intervention in late childhood and adolescence. It is vital for researchers to broaden the evidence base for addressing chronic malnutrition through multiple life stages, and for program implementers to explore effective, sustainable ways of reaching the most vulnerable populations.

Estimates of burden and consequences of infants born small for gestational age in low and middle income countries with INTERGROWTH-21(st) standard: analysis of CHERG datasets.

Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21st birth weight standard. Design Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21st birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated. Setting CHERG birth cohorts from 14 population based sites in low and middle income countries. Main outcome measures In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%. Results In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight (<2500 g) and 1.5 million (0.9 to 2.6) were preterm. In low and middle income countries, an estimated 606 500 (495 000 to 773 000) neonatal deaths were attributable to infants born small for gestational age, 21.9% of all neonatal deaths. The largest burden was in South Asia, where the prevalence was the highest (34%); about 26% of neonatal deaths were attributable to infants born small for gestational age. Reduction of the prevalence of small for gestational age from 19.3% to 10.0% in these countries could reduce neonatal deaths by 9.2% (254 600 neonatal deaths; 164 800 to 449 700). Conclusions In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countries

International standards for symphysis-fundal height based on serial measurements from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project: prospective cohort study in eight countries

Objective To create international symphysis-fundal height standards derived from pregnancies of healthy women with good maternal and perinatal outcomes. Design Prospective longitudinal observational study. Setting Eight geographically diverse urban regions in Brazil, China, India, Italy, Kenya, Oman, United Kingdom, and United States. Participants Healthy, well nourished pregnant women enrolled into the Fetal Growth Longitudinal Study component of the INTERGROWTH-21st Project at 9-14 weeks’ gestation, and followed up until birth. Main outcome measures Symphysis-fundal height was measured every five weeks from 14 weeks’ gestation until birth using standardised methods and dedicated research staff who were blinded to the symphysis-fundal height measurements by turning the tape measure so that numbers were not visible during examination. The best fitting curve was selected using second degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. Results Of 13 108 women screened in the first trimester, 4607 (35.1%) met the study entry criteria. Of the eligible women, 4321 (93.8%) had pregnancies without major complications and delivered live singletons without congenital malformations. The median number of symphysis-fundal height measurements was 5.0 (range 1-7); 3976 (92.0%) women had four or more measurements. Symphysis-fundal height measurements increased almost linearly with gestational age; data were used to determine fitted 3rd, 50th, and 97th centile curves, which showed excellent agreement with observed values. Conclusions This study presents international standards to measure symphysis-fundal height as a first level screening tool for fetal growth disturbances.

Implementation of the INTERGROWTH-21stProject in Brazil: The INTERGROWTH-21stProject in Brazil

Please cite this paper as: Silveira M, Barros F, Sclowitz I, Domingues M, Mota D, Fonseca S, Mitidieri A, Leston A, Knight H, Cheikh Ismail L, for the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH‐21st). Implementation of the INTERGROWTH‐21st Project in Brazil. BJOG 2013; 120 (Suppl. 2): 81–86.

Secular trends in smoking during pregnancy according to income and ethnic group: four population-based perinatal surveys in a Brazilian city

Objectives To assess socioeconomic and ethnic inequalities in smoking during pregnancy over three decades (1982–2011). Setting Population-based study in Pelotas City, Brazil. Participants All urban women giving birth in the city hospitals in 1982 (5909), 1993 (5223) and 2004 (4201), plus all urban and rural women delivering from January 2011 to April 2012 (6275). Primary outcome Self-reported smoking during pregnancy. Results The prevalence of smoking during pregnancy fell from 35.7% in 1982 to 21.0% in 2011. In each survey, prevalence decreased with increasing income (p<0.001). In the poorest quintile, smoking fell by 27.4% in the period studied compared to 67.1% in the wealthiest quintile. In all surveys, prevalence was lower among white women than among those who classified themselves as black or brown (p<0.001). Over time, smoking declined by 50.0% among the former and 30.7% among the latter. Absolute and relative inequalities both increased over time. Conclusions The reduction in smoking during pregnancy was primarily due to a decline among white, high-income women. Further efforts are needed to reduce smoking among all population groups.

LBW and IUGR temporal trend in 4 population-based birth cohorts: the role of economic inequality

BackgroundLow/medium income countries, with health inequalities present high rates of neonates having low birthweight and/or are small for the gestational age. This study aims to analyze the absolute and relative income inequality in the occurrence of low birthweight and small size for gestational age among neonates in four birth cohorts from southern Brazil in 1982, 1993, 2004, and 2011.MethodsThe main exhibit was monthly family income. The outcomes were birth with low birthweight or small for the gestational age. The inequalities were calculated using the Slope Index of Inequality and the Relative Index of Inequality adjusted for maternal skin color, schooling, age, and marital status.ResultsIn all birth cohorts, poorer mothers were at greater odds of having neonates with low birthweight or small for the gestational age. There was a tendency to decrease the prevalence of small for gestational age in poorer families associated with the reduction of inequalities over the past decades, which was not observed regarding low birthweight.ConclusionsEconomic inequalities occurred in neonates with low birthweight and with intrauterine growth restriction in the four studies, with a higher incidence of inadequate neonatal outcomes in the poorer families.