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

Background

Short 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).

Methods

We 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.

Results

Birth 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.

Conclusions

Birth 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.

     

Effects of maternal education, age, and parity on fatal infant accidents

Accidents are a major cause of death among children. Using computerized linked birth and death record information, this study examined the relationship of selected parental factors to the risk of infant accidental death. The analyses suggest that maternal age and education are inversely related to infant accident mortality while mother's parity is directly related. Accident mortality rate differentials by educational level were more evident for certain categories of accidents.     

The influence of maternal age on very preterm birth of twins: differential effects by parity

For singleton births, parity can modify the effect of maternal age on birth outcomes such as low birthweight and preterm birth; however, it is unknown whether this relationship exists for twin births. As the rate of twin births increases among older women, it is important to understand how parity may influence the relationship between maternal age and adverse birth outcomes. The NCHS Matched Multiple Birth Data Set, which contains all twin births in the USA from 1995 to 1998, was analysed. Parity was grouped into two levels (primiparous--no prior live births, and multiparous--at least one prior live birth), and maternal age was divided into the following groups: 20-24, 25-29, 30-34, 35-39, and 40 years or more. Very preterm birth was defined as births occurring before 33 weeks. Logistic regression was used to obtain odds ratios (OR) to estimate the risk of very preterm birth, and to determine the relationships between parity, maternal age, and very preterm birth. Among primiparae, women 40 years and older had a reduced risk of very preterm birth compared with women of 25-29 years (OR 0.74 [95% CI=0.66, 0.84]). Among multiparae, women 40 years and older had the same risk of very preterm birth compared with women of 25-29 years (OR 1.00 [95% CI=0.90, 1.12]). However, stratification by education revealed that the age gradient was limited to women with >12 years education among primiparae. The effect of maternal age on very preterm birth of twins differs according to parity. To some extent, that effect is further modified by education. Therefore, future analyses of maternal age and twin birth outcomes should account for measures of obstetric history and other factors, which may influence these results.     

Vitamin D during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis

Vitamin D has well-defined classical functions related to calcium metabolism and bone health but also has non-classical effects that may influence other aspects of health. There has been considerable recent interest in the role of vitamin D on outcomes related to pregnancy and young child health but few efforts have been made to systematically consolidate this evidence to inform the research and policy agenda for low-income countries. A systematic review was undertaken to identify intervention and observational studies of vitamin D supplementation, intake or status (25-hydroxy-vitamin D) during pregnancy on perinatal and infant health outcomes. Data from trials and observational studies isolating the effect of vitamin D supplementation and intake were extracted and study quality was evaluated. Meta-analysis was used to pool effect estimates. We identified five randomised trials with outcomes of relevance to our review. All had small sample size and dosage amount, duration and frequency varied as did the ability to correct deficiency. Pooled analysis of trials using fixed-effects models suggested protective effects of supplementation on low birthweight (three trials, risk ratio (RR) = 0.40 [95% confidence interval (CI) 0.23, 0.71]) and non-significant but suggestive effects of daily supplementation on small-for-gestational age (two trials, RR = 0.67 [0.40, 1.11]). No effect on preterm delivery (<37 weeks) was evident (two trials, RR = 0.77 [0.35, 1.66]). Little evidence from trials exists to evaluate the effect of vitamin D supplementation during pregnancy on maternal, perinatal or infant health outcomes. Based on both trials and observational studies, we recommend that future research explore small-for-gestational age, preterm delivery, pre-eclampsia, and maternal and childhood infections, as outcomes of interest. Trials should focus on populations with a high prevalence of vitamin D deficiency, explore the relevance of timing of supplementation, and the dosage used in such trials should be sufficient to correct deficiency.     

Medically induced preterm birth and the associations between prenatal care and infant mortality

PurposeDuring the last 30 years, the use of prenatal care, both the proportion of women receiving the recommended number of visits and the average number of visits, has increased substantially. Although infant mortality has decreased, the incidence of preterm birth has increased. We hypothesized that prenatal care may lead to lower infant mortality in part by increasing the detection of obstetrical problems for which the clinical response may be to medically induce preterm birth.MethodsWe examined whether medically induced preterm birth mediates the association between prenatal care and infant mortality by using newly developed methods for mediation analysis. Data are the cohort version of the national linked birth certificate and infant death data for 2003 births. Analyses were adjusted for maternal sociodemographic, geographic, and health characteristics.ResultsReceiving more prenatal care visits than recommended was associated with medically induced preterm birth (odds ratio [OR], 2.44; 95% confidence interval [95% CI], 2.40–2.49) compared with fewer visits than recommended). Medically induced preterm birth was itself associated with greater infant mortality (OR, 5.08; 95% CI, 4.61–5.60) but that association was weaker among women receiving extra prenatal care visits (OR 3.08; 95% CI, 2.88–3.30) compared with women receiving the recommended number of visits or fewer.ConclusionsThese analyses suggest that some of the benefit of prenatal care in terms of infant mortality may be in part due to medically induced preterm birth. If so, the use of preterm birth rates as a metric for tracking birth policy and outcomes could be misleading.     

Young maternal age and infant mortality: the role of low birth weight

In 1980, there were 562,330 babies born in the United States to teenage mothers (19 years of age or younger). The offspring of teenage mothers have long been known to be at increased risk of infant mortality, largely because of their high prevalence of low birth weight (less than 2,500 grams). We used data from the National Infant Mortality Surveillance (NIMS) project to examine the effect of young maternal age and low birth weight on infant mortality among infants born in 1980 to U.S. residents. This analysis was restricted to single-delivery babies who were either black or white, who were born to mothers ages 10-29 years, and who were born in one of 48 States or the District of Columbia. Included were 2,527,813 births and 28,499 deaths (data from Maine and Texas were excluded for technical reasons). Direct standardization was used to calculate the relative risks, adjusted for birth weight, of neonatal mortality (less than 28 days of life) and postneonatal mortality (28 days to less than 1 year of life) by race and maternal age. There was a strong association between young maternal age and high infant mortality and between young maternal age and a high prevalence of low birth weight. Neonatal mortality declined steadily with increasing maternal age. After adjusting for birth weight, the race-specific relative risks for babies born to mothers less than 16 years of age were still elevated from 11 to 40 percent, compared with babies born to mothers 25-29 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vitamin A and carotenoids during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis

Vitamin A (VA) deficiency during pregnancy is common in low-income countries and a growing number of intervention trials have examined the effects of supplementation during pregnancy on maternal, perinatal and infant health outcomes. We systematically reviewed the literature to identify trials isolating the effects of VA or carotenoid supplementation during pregnancy on maternal, fetal, neonatal and early infant health outcomes. Meta-analysis was used to pool effect estimates for outcomes with more than one comparable study. We used GRADE criteria to assess the quality of individual studies and the level of evidence available for each outcome. We identified 23 eligible trials of which 17 had suitable quality for inclusion in meta-analyses. VA or beta-carotene (βC) supplementation during pregnancy did not have a significant overall effect on birthweight indicators, preterm birth, stillbirth, miscarriage or fetal loss. Among HIV-positive women, supplementation was protective against low birthweight (<2.5 kg) [risk ratio (RR) = 0.79 [95% confidence interval (CI) 0.64, 0.99]], but no significant effects on preterm delivery or small-for-gestational age were observed. Pooled analysis of the results of three large randomised trials found no effects of VA supplementation on neonatal/infant mortality, or pregnancy-related maternal mortality (random-effects RR = 0.86 [0.60, 1.24]) although high heterogeneity was observed in the maternal mortality estimate (I(2) = 74%, P = 0.02). VA supplementation during pregnancy was found to improve haemoglobin levels and reduce anaemia risk (<11.0 g/dL) during pregnancy (random-effects RR = 0.81 [0.69, 0.94]), also with high heterogeneity (I(2) = 52%, P = 0.04). We found no effect of VA/βC supplementation on mother-to-child HIV transmission in pooled analysis, although some evidence suggests that it may increase transmission. There is little consistent evidence of benefit of maternal supplementation with VA or βC during pregnancy on maternal or infant mortality. While there may be beneficial effects for certain outcomes, there may also be potential for harm through increased HIV transmission in some populations.     

The influence of maternal age, birth order and socioeconomic status on infant mortality in Chile.

In Chile between 1969 and 1974 the birth rate declined by 10 per cent and the infant mortality rate by 18.6 per cent. In 1974 there were proportionately fewer births at high birth order than in 1969. Such births carry significantly higher risk to the infant in both the neonatal and postneonatal period of life. Comparison of data from urban areas of high and low socioeconomic status yield similar findings.     

An assessment of the effects of maternal age and parity in different components of perinatal mortality

Perinatal mortality has several components which may have distinct epidemiologic features. In an investigation of the total singleton birth population of New York City in 1976-1978 (n = 320,726), the authors divided perinatal mortality into four components: late fetal deaths that occurred before labor (late antepartum fetal deaths), fetal deaths during labor (intrapartum fetal deaths), neonatal deaths, and perinatal deaths attributed to congenital anomalies, and they assessed the relation of each of these to maternal age and parity, controlling for relevant confounding factors. In analyses which controlled for prior fetal loss, type of service (public vs. private), race, marital status, and mother's educational attainment in a multiple logistic regression model, the authors found that: 1) increasing maternal age was strongly associated with antepartum fetal deaths but not with intrapartum fetal deaths, while older maternal age was also associated with perinatal deaths attributed to congenital anomalies; 2) high parity bore a strong relationship to intrapartum fetal deaths, but none to antepartum fetal deaths, neonatal deaths, or congenital anomaly deaths; and 3) for neonatal death, there was a statistically significant (p less than 0.001) interaction between parity and age such that mothers over 34 years old having their first birth were at especially high risk.     

Relationship of birthweight,maternal nutrition and infant mortality

A longitudinal study of the social and biological determinants of physical growth and mental development in rural Guatemala was started in 1969. A program was launched involving supplementation of pregnant mothers with a protein and calorie supplement ("atole") in 2 villages and another calorie supplement ("fresco") in 2 other villages. This paper presents an integrated quantitative approach to the analysis of data collected in the maternal supplementation program using 2 examples. The first example compares the effects of maternal height and weight at conception, and maternal caloric supplementation during pregnancy on birthweight. It was found that maternal childhood nutrition is as important a determinant of birthweight as is caloric supplementation during pregnancy. Similarly, the nutritional status of the mother during conception is as powerful a determinant of birthweight as is caloric supplementation during pregnancy. Past obstetrical history and maternal age do not affect these interrelationships among birthweight and maternal height, weight at conception, and maternal supplementation. The second example involves a consideration of postnatal function of the child, as well as several prenatal factors which affect infant mortality. Infant mortality in the study villages was found to be 4 times greater for babies with birthweight of 2.5 kg or less at term ("small for dates" babies; infant mortality rate, 121/1,000) than for heavier babies (infant mortality rate, 30/1000) (p0.05). By increasing maternal calorie supplementation during pregnancy, the number of babies weighing 2.5 kg or less was reduced from 20% among babies born to mothers ingesting less than 5000 calories during pregnancy to 5% among babies born to mothers who consume more than 20,000 calories during pregnancy. The findings suggest that village infant mortality can be lowered, and the birth of "small for dates" babies prevented by ensuring adequate levels of maternal nutrition during pregnancy. Efforts to improve maternal nutrition should start in childhood for optimum infant survival.     

孕期增重与早产关联的流行病学分析

妊娠期孕妇的睡眠模式发生明显改变,睡眠时间异常、睡眠质量差等问题尤为突出。不健康的睡眠模式增加了不良妊娠结局的发生风险,早产作为最常见的不良妊娠结局,是导致新生儿患病和死亡的最主要原因。笔者通过文献复习,对孕妇睡眠现状进行简述,同时从睡眠时间和睡眠质量2个方面概述睡眠与早产之间的关系。在未来研究中,应加强对孕妇睡眠情况的关注,制定有效的干预措施,指导孕妇进行健康睡眠。     

The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity

Objective

To analyse preterm birth rates worldwide to assess the incidence of this public health problem, map the regional distribution of preterm births and gain insight into existing assessment strategies.

Methods

Data on preterm birth rates worldwide were extracted during a previous systematic review of published and unpublished data on maternal mortality and morbidity reported between 1997 and 2002. Those data were supplemented through a complementary search covering the period 2003–2007. Region-specific multiple regression models were used to estimate the preterm birth rates for countries with no data.

Findings

We estimated that in 2005, 12.9 million births, or 9.6% of all births worldwide, were preterm. Approximately 11 million (85%) of these preterm births were concentrated in Africa and Asia, while about 0.5 million occurred in each of Europe and North America (excluding Mexico) and 0.9 million in Latin America and the Caribbean. The highest rates of preterm birth were in Africa and North America (11.9% and 10.6% of all births, respectively), and the lowest were in Europe (6.2%).

Conclusion

Preterm birth is an important perinatal health problem across the globe. Developing countries, especially those in Africa and southern Asia, incur the highest burden in terms of absolute numbers, although a high rate is also observed in North America. A better understanding of the causes of preterm birth and improved estimates of the incidence of preterm birth at the country level are needed to improve access to effective obstetric and neonatal care.     

宁海县2010—2015年5岁以下儿童死亡原因分析

目的探讨妊娠中期(孕24~28周)无症状孕妇血清IL-1、IL-6、IL-8、TNF-a及CRH浓度与早产的关系。方法选择2015年1月—2017年12月在上海市浦东新区妇幼保健院定期产检,孕24~28周无症状的孕妇,抽取其静脉血,采样冻存待测。随访其妊娠结局,根据妊娠结局选择早产组100例,包括自发性早产71例和未足月胎膜早破29例,并选择同期足月分娩者100例为对照组。采用ELISA法检测血清IL-1、IL-6、IL-8、TNF-a和CRH的浓度。两组产后胎膜送病理检查,判断有无绒毛膜羊膜炎。结果早产组孕24~28周血清IL-1、IL-6、IL-8浓度高于对照组(P < 0.05), 血清TNF-a、CRH浓度无明显升高(P>0.05)。早产绒毛膜羊膜炎组血清IL-6、IL-8浓度高于早产非绒毛膜羊膜炎组和对照组,早产非绒毛膜羊膜炎组和对照组差异无统计学意义(P < 0.05);早产绒毛膜羊膜炎组的血清IL-1浓度与早产非绒毛膜羊膜炎组比较,差异无统计学意义,但明显高于对照组(P < 0.05)。3组间血清TNF-a和CRH的浓度差异无统计学意义(P>0.05)。血清IL-1预测早产的ROC曲线下面积(AUC)为0.843,最佳界值为10.699 pg/mL;IL-6的AUC为0.675,最佳界值为104.411 pg/mL;IL-8的AUC为0.55,最佳界值为65.496 pg/mL。结论孕24~28周无症状孕妇的血清IL-1、IL-6、IL-8水平对预测早产有一定的价值。     

The effects of race, residence, and prenatal care on the relationship of maternal age to neonatal mortality.

This population-based study explores whether excessive neonatal mortality rates (NMRs) among infants with teenage mothers are attributable to young maternal age or to a translation of environmental disadvantage into reproductive disadvantage. First births from the 1976-79 linked birth and infant death registers for three states are analyzed. The data set is sufficiently large (305,907 births) to measure maternal age in fine gradations while including several control variables in logit analyses. The associations of racial identification and prenatal care with low birthweight, short gestation, and neonatal mortality overshadow and confound the association between teenage and poor outcome. At every maternal age, higher NMRs are observed for Blacks compared to Whites. The hypothesis that excessive neonatal mortality among Blacks is due to the greater frequency of teenage childbearing among Blacks is refuted. Indeed, unlike White, Black primiparae above age 23 experience higher NMRs than most Black or White teenagers. These results suggest that teenage maternity is not the primary causal agent of all of the problems with which it is associated.     

The association of maternal smoking with age and cause of infant death

Linked birth certificate and infant death certificate data from Missouri for 1979-1983 were used to explore the association of maternal smoking with age and cause of infant death. The data included 305,730 singleton white livebirths, of which 2,720 resulted in infant deaths. Using multiple logistic regression to control for the confounding effects of maternal age, parity, marital status, and education, the authors found that smoking was associated with both neonatal and post-neonatal mortality and with each cause of death except congenital anomalies. The adjusted odds ratio for smoking was higher for postneonatal deaths than neonatal deaths and was particularly high for two causes: respiratory disease (odds ratio = 3.4) and sudden infant death syndrome (odds ratio = 1.9). A moderate odds ratio (about 1.4) was found for causes attributed to the International Classification of Diseases, 9th Revision Perinatal Conditions Chapter. Although the associations for neonatal deaths and perinatal conditions were partially attributable to the effect of maternal smoking in lowering birth weight, virtually none of the excess respiratory mortality and sudden infant death syndrome mortality among the offspring of smokers was attributable to birth weight differences between the infants of smokers and nonsmokers. This suggests that respiratory deaths and sudden infant death syndrome deaths may be related to the effect of passive exposure of the infant to smoke after birth.     

不同年龄组新型冠状病毒肺炎患者临床特征分析

  目的   比较新冠病毒德尔塔变异株、奥密克戎变异株BA.1和BA.2在老年感染者中临床表现和严重程度差异。  方法   收集2022年河南省4次大规模新冠肺炎本土疫情中 ≥ 60岁老年感染者的社会人口学信息和发病资料,采用χ²、Fisher精确概率法比较不同变异株感染者发病差异,使用多因素logistic回归分析新冠肺炎重型或危重型的影响因素。  结果   共纳入老年新冠病毒感染者234例,其中德尔塔变异株感染者118例,奥密克戎变异株感染者116例（BA.1 36例、BA.2 80例）;56.8 %的感染者为女性,47.6 %有基础性疾病,88.0 %接种了新冠病毒疫苗;德尔塔变异株感染者出现临床症状的比例高于奥密克戎变异株（34.7 % vs. 19.0 %,χ² = 7.404,P = 0.007）,临床表现均以咳嗽、咽痛、咽干等上呼吸道症状和发热、乏力等全身症状为主;德尔塔变异株感染者发展成重型或危重型的比例高于奥密克戎变异株感染者（12.7 % vs. 1.7 %,P = 0.002）,多因素logistic回归分析结果显示,感染德尔塔变异株（OR = 5.7,95 % CI = 1.1～31.2）,≥ 80岁年龄组（OR = 8.4,95 % CI = 2.0～34.4）,存在运动障碍（OR = 5.3,95 % CI = 1.5～18.3）和糖尿病（OR = 5.7,95 % CI = 1.1～31.3）是 ≥ 60岁老年感染者发展成新冠肺炎重型或危重型的危险因素。  结论   ≥ 60岁老年人群感染不同新冠病毒变异株,在临床症状、重型或危重型发生风险上存在差异,感染德尔塔变异株、高龄和患有基础性疾病是发展成重型或危重型的危险因素。     

The effects of maternal smoking on fetal and infant mortality

Although maternal cigarette smoking has been shown to reduce the birth weight of an infant, previous findings on the relation between smoking and fetal and infant mortality have been inconsistent. This study used the largest data base ever available (360,000 birth, 2,500 fetal death, and 3,800 infant death certificates for Missouri residents during 1979-1983) to assess the impact of smoking on fetal and infant mortality. Multiple logistic regression was used to estimate the joint effects of maternal smoking, age, parity, education, marital status, and race on total mortality (infant plus fetal deaths). Compared with nonsmoking women having their first birth, women who smoked less than one pack of cigarettes per day had a 25% greater risk of mortality, and those who smoked one or more packs per day had a 56% greater risk. Among women having their second or higher birth, smokers experienced 30% greater mortality than nonsmokers, but there was no difference by amount smoked. The prevalence of smoking in this population was 30%. It was estimated that if all pregnant women stopped smoking, the number of fetal and infant deaths would be reduced by approximately 10%. The higher rate of mortality among blacks compared with whites could not be attributed to differences in smoking or the other four maternal characteristics studied. In fact, the black-white difference was greater among low-risk women (e.g., married multiparas aged 20 and over with high education) than among high-risk women (e.g., unmarried teenagers with low education).