Effects of Maternal Pregnancy Intention,Depressive Symptoms and Social Support on Risk of Low Birth Weight: A Prospective Study from Southwestern Ethiopia

Background

Low birth weight (LBW) is the principal risk factor for neonatal and infant mortality in developing countries. This study examines the effects of unwanted pregnancy, prenatal depression and social support on the risk of low birth weight in rural southwestern Ethiopia. We hypothesized that unwanted pregnancy and prenatal depression increase the risk of low birth weight, while social support mediates this association.

Methods

Data for the study comes from a prospective study in which women were followed from pregnancy through to delivery. Six hundred twenty two women were followed and 537 birth weights were measured within 72 hours. Multivariable log binomial regression was used to model the risk of low birth weight.

Results

The mean birth weight was 2989 grams (SD±504 grams), and the incidence of LBW was 17.88%. The mean birth weight of babies after unwanted pregnancy was 114 g lower compared to births from intended pregnancy. Similarly, mean birth weight for babies among women with symptoms of antenatal depression was 116 grams lower. Results of unadjusted log-binomial regression showed that unwanted pregnancy, prenatal depression and social support were associated with LBW. The relationship between antenatal depressive symptoms and LBW was mediated by the presence of social support, while the association between LBW and unwanted pregnancy remained after multivariable adjustment.

Conclusion

The incidence of low birth weight is high in the study area. Poverty, nonuse of antenatal care, low social support and unwanted pregnancy contribute to this high incidence of low birth weight. Hence, identifying women’s pregnancy intention during antenatal care visits, and providing appropriate counseling and social support will help improve birth outcomes.     

The COVID-19 pandemic and birth outcomes in 2020: The role of prenatal care and other channels

We use national birth data to assess the associations between the COVID-19 pandemic during 2020 and birth outcomes in Uruguay. Employing interrupted time series difference-in-differences techniques, we find mixed results, with some pregnancies showing increases in the likelihood of very preterm or very-low-weight births, and some others showing decreases in the incidence of moderate prematurity and moderate low birth weight. Adverse outcomes are more likely among women with low education, women with previous children, and with risk factors, such as smoking or being older than 34. We observe improvements in health at birth for children of non-smokers, women younger than 35, and women with no other children. We underscore the role of health care by showing that women in the private sector, who suffered the strongest contraction in face-to-face prenatal care use, experienced more adverse birth outcomes. Our results also suggest that the economic recession and an increased burden of childcare were behind the increases in preterm and very-low-weight births. Because pollution is an unlikely channel for the positive results, we hypothesize that for some pregnancies, the pandemic improved the intrauterine habitat by leading to a quieter and healthier lifestyle.     

Congenital malformations in Utah

The rate of malformed children in Utah of 11.7 per 1,000 liver births, derived from 128,857 birth certificates, ws not high compared with other non-Utah studies. Rates of selected malformations also were not high. The rate of malformed children varied by county of residence. San Juan County reported the highest percentage of mothers receiving late or infrequent prenatal care, the lowest mean level of public education, and the highest rate of malformed children in the state. The rate was not significantly associated with the large population of Indians residing in that county since by controlling for residence, the variation by race was eliminated. The overall rate was positively associated with maternal age rimarily due to an increased frequency of Down's syndrome. The impact of the "maternal age effect" on the state malformation rate, however, was not large. By controlling for maternal age, the slight association between increased rate of malformed children and increasing birth order was eliminated. The rate of malformed children was higher for parents having a low level of education, infrequent prenatal care, or who were not married. There was also a strong negative association of birth weight with the rate of malformation. Analysis of rates of selected malformations suggested that the low birth weight was a sequela to intrauterine growth retardation caused by severe congenital malformation. The validity and etiologic implications of these results await further investigation.     

Impact of maternal age on birth outcomes: a population-based study of primiparous Brazilian women in the city of São Paulo

The aim of this study is to analyse the impact of maternal age at first birth on low birth weight, preterm birth and low Apgar scores at one minute and at five minutes among live births delivered to primiparous Brazilian women in the city of S?o Paulo. Analyses were based on 73,820 birth records from the 1998 birth cohort. Logistic regression was used to assess the association between maternal age and each outcome variable, controlling for the following risk factors: delivery mode, plurality, sex, maternal education, number of prior losses, prenatal care, race, parity and community development. Maternal ages below 20 and above 30 years were significantly associated with the risks of low birth weight and preterm birth, but no association was found between maternal ages and Apgar score, with the exception that ages 15-19 reduced the odds of a low one-minute score. Even though this result seems to be inconsistent, low birth weight, preterm birth and low Apgar scores measure different dimensions of newborn well-being, and the association of each measure with maternal age is expected to diverge.     

Association of paternal alcohol use with gestational age and birth weight.

Paternal alcohol use has been associated with a number of adverse reproductive outcomes in laboratory animals and there is one epidemiologic report of a detrimental effect on infant birth weight. To expand the epidemiologic evidence, data from the Child Health and Development Studies were analyzed. Data collected from the onset of prenatal care in 10,232 women enrolled in the Kaiser Foundation Health Plan and residing in the San Francisco East Bay area between June 1959 and September 1966 were available, including information on the mother's report of paternal alcohol consumption and a number of potential confounders. Pregnancy outcomes included preterm delivery (< 37 weeks completed gestation), moderately low birth weight (1,501-2,500 g), very low birth weight (< or = 1,500 g), small-for-gestational-age (< 10th percentile of weight for gestational age), and mean birth weight. Paternal alcohol use, analyzed in intervals from 0 to 2.0 or more drinks per day, showed no association with any of the outcomes of interest. Adjusted prevalence odds ratios ranged from 0.7 to 1.5, with no indication of a monotonic dose-response gradient. Mean birth weight was also virtually unrelated to paternal alcohol use. Compared with the earlier report, this population had a very modest level of alcohol consumption. Nonetheless, within the range that was studied there appears to be no association between paternal alcohol use and birth outcome.     

Prenatal Care Utilization for Mothers from Low-Income Areas of New Mexico, 1989–1999

Background

Prenatal care is considered to be an important component of primary health care. Our study compared prenatal care utilization and rates of adverse birth outcomes for mothers from low- and higher-income areas of New Mexico between 1989 and 1999.

Methodology/Principal Findings

Prenatal care indicators included the number of prenatal care visits and the first month of prenatal care. Birth outcome indicators included low birth weight, premature birth, and births linked with death certificates. The results of our study indicated that mothers from low-income areas started their prenatal care significantly later in their pregnancies between 1989 and 1999, and had significantly fewer prenatal visits between 1989 and 1997. For the most part, there were not significant differences in birth outcome indicators between income groupings.

Conclusions/Significance

These findings suggest that while mothers from low-income areas received lower levels of prenatal care, they did not experience a higher level of adverse birth outcomes.     

Prenatal care demand and its effects on birth outcomes by birth defect status in Argentina

Our objective was to identify determinants of prenatal care demand and evaluate the effects of this demand on low birth weight and preterm birth. Delay in initiating prenatal care was modeled as a function of pregnancy risk indicators, enabling factors, and regional characteristics. Conditional maximum likelihood (CML) estimation was used to model self-selection into prenatal care use when estimating its effectiveness. Birth registry data was collected post delivery on infants with and without common birth defects born in 1995-2002 in Argentina using a standard procedure. Several maternal health and fertility indicators had significant effects on prenatal care use. In the group without birth defects, prenatal care delay increased significantly LBW and preterm birth when accounting for self-selection using the CML model but not in the standard probit model. Prenatal care was found to be ineffective on average in the birth defect group. The self-selection of higher risk women into earlier initiation of prenatal care resulted in underestimation of prenatal care effectiveness when using a standard probit model with several covariates. Large improvements in birth outcomes are suggested with earlier initiation of prenatal care for pregnancies uncomplicated with birth defects in Argentina, implying large opportunity costs from the long waiting time observed in this sample (about 17 weeks on average). The suggested ineffectiveness for pregnancies complicated with common birth defects deserves further research.     

Birth weight, maternal age, and education: new observations from Connecticut and Virginia

It has been well established that increased maternal education, income, and social status contribute to increased birth weight, as well as reduced risk for low or very low birth weight offspring. However, there remains controversy about the mechanism(s) for this effect, as well as the interactions between these factors, maternal age, and race. Presented here is the analysis of a large, recent sample of over 20,000 consecutive live births in 12 hospitals, about half in Connecticut and half in Virginia, including a maternal population that is educationally and racially diverse. Although information on potentially relevant details such as prenatal care, smoking, occupation, and neighborhood is lacking the data set, there is sufficient information to explore the previously noted strong effect of maternal education on birth weight, as well as the large racial difference in outcome at every educational level after adjustment for the effects of age, marital status, state of residence, and gender of the offspring. However, this relationship was not monotonic, and there were differences in the effect between the white and black families, with black women showing a linear and consistent benefit from education across the range, while whites show a sharp benefit from completion of primary education, less from subsequent schooling. A surprising result was the apparent negative impact of very advanced education (>16 years), with lowered birth weights and higher risk of low birth weight offspring in the women with post-college training. The data also shed some addition light on the effect of age and birth weight. Whites show established improvement in birth outcome to about age 30, with slight decline thereafter, whereas in blacks there was progressive decline in birth weight with rising age starting in adolescence, as previously demonstrated by Geronimus. An additional unexpected observation was a sizable difference between births in Connecticut (larger, fewer low birth weight) than Virginia, correcting for all other covariates. It is hypothesized that this may reflect differences in services used, prenatal care in particular given similarities in smoking rates and other predictors. Because of the non-representativeness of and the limited information available in the present study, the conclusions should be taken as hypotheses for further research rather than definitive.     

Low-birth-weight effects of demographic and socioeconomic variables and prenatal care in Pima County,Arizona.

Low birth weight is the major determinant of infant mortality. Continuing declines in infant mortality in the United States are due to the use of neonatal intensive care services; less progress has been made toward preventing low birth weight. I examined how the demographic, socioeconomic, and health services use variables affected rates of low birth weights in Pima County, Arizona, in 1985. Women at greatest risk of having the smallest infants were those younger than 21 years and those with fewer than 6 prenatal visits. Nulliparous women with fewer than 6 prenatal visits showed a still greater risk of having an infant of low birth weight. Women without medical insurance coverage had babies with the lowest mean birth weights, as well as significantly fewer prenatal visits. As the number of uninsured in the United States increases, the effect of lack of insurance among pregnant women becomes increasingly important. To prevent low-weight births, comprehensive maternity care services must be available to all pregnant women regardless of ability to pay.     

Coadaptation of prenatal and postnatal maternal effects

In a wide variety of species, a female's age of first reproduction influences offspring size and survival, suggesting that there exists an optimal timing of reproduction. Mothers in many species also influence offspring size and survival after birth through variation in parental care. We experimentally separated these effects in the burying beetle Nicrophorus vespilloides to test for coadaptation between prenatal and postnatal maternal effects associated with age at first reproduction. Females that reproduced early produced offspring with lower birth weight. The amount of parental care depended on the age of first reproduction of the caretaker, as did the extent of offspring begging. As predicted for a coadaptation of maternal effects, prenatal and postnatal effects were opposite for different-aged mothers, and larval weight gain and survival was greatest when the age of the caretaker and birth mother matched. Thus, prenatal effects intrinsically associated with age of first reproduction can be ameliorated by innate plasticity in postnatal care. A coadaptation of prenatal and postnatal maternal effects may evolve to allow variable timing of the first reproductive attempt. Such a coadaptation might be particularly valuable when females are constrained from reproducing at an optimal age, as, for example, in species that breed on scarce and unpredictable resources.     

Stability of the Association between Birth Weight and Childhood Overweight during the Development of the Obesity Epidemic

Objective: To assess whether changes in the birth weight distribution or changes in the association of birth weight with the later risk of childhood overweight have contributed to the development of the obesity epidemic. Research Methods and Procedures: A Danish population‐based cohort study of 124,615 girls and 128,346 boys (ages 6 to 13 years), born between 1936 and 1983, were studied. Birth weight and annual measurements of height and weight were obtained from school health records. Overweight was defined by BMI in relation to internationally accepted criteria. The relative risk of being overweight by birth weight was calculated separately for each age, sex, and time period. Results: The birth weight distribution remained relatively stable over time. Compared with children with a birth weight of 3.0 to 3.5 kg, the risk of overweight increased consistently with each increase in birth weight category among girls and boys and at all ages between 6 and 13 years. Furthermore, the association between birth weight and increased risk of overweight in childhood remained stable across a 48‐year period. Discussion: The increase in the prevalence of overweight could not be explained by time trends in the distribution of birth weight or by changes in the association between birth weight and the later risk of overweight over time. This implies that, unless the prenatal environment influences the later risk of overweight without increasing birth weight, the environmental influences contributing to the obesity epidemic in children of school age operate in the early postnatal period.     

Rapporteur report: Epidemiology

Three talks were presented in the session on “Epidemiology”. The first talk was a review of prenatal studies. The second talk presented epidemiological evidence from prenatal studies. The third talk presented general issues regarding the planning of an epidemiological study. It was noted that epidemiological studies of prenatal exposures use data from the early 1980s when ultrasound was first introduced for foetal scans. These studies did not show associations between prenatal ultrasound scanning and childhood cancer, reduced birth weight, impaired childhood growth or neurological development in childhood. However, there was a possible association between prenatal ultrasound scanning and left-handedness in boys. The aetiology of this association remains uncertain.     

Prenatal Care in Combination with Maternal Educational Level Has a Synergetic Effect on the Risk of Neonatal Low Birth Weight: New Findings in a Retrospective Cohort Study in Kunshan City,China

Objectives

To investigate the dose-response relationship and synergetic effect of the maternal educational level and two measures of prenatal care on neonatal low birth weight (LBW) risk.

Methods

Data were derived from the Perinatal Health Care Surveillance System (PHCSS) from January 2001 to September 2009 in Kunshan City, Jiangsu province, eastern China, which included data on 31412 women with a normal birth weight delivery and 640 women with a LBW delivery. Logistic modelling was performed to estimate the association including the joint effects with odds ratio (OR) and 95% confidence interval (CI) between the prenatal care measures and LBW risk after adjusting for the potential confounders. The dose-response relationship between the number of prenatal care visits and the risk of LBW was investigated by modeling the quantitative exposure with restricted cubic splines (RCS).

Results

There was a significant synergetic effect on the LBW risk between maternal educational attainment and the number of prenatal care visits (χ² = 4.98, P = 0.0257), whereas no significant maternal educational attainment interaction was found with the week of initiation of prenatal care after adjusting for relevant confounding factors (χ² = 2.04, P = 0.1530), and the LBW risk displayed a ‘U-shape’ curve tendency among the different number of prenatal care visits (P for nonlinearity = 0.0002) using RCS. In particular, the ORs were approaching the curve’s bottom when the women had 9 or 10 prenatal care visits. Comparing with 5 prenatal care visits, the ORs and 95%CI of LBW risk for 7, 9, 11 and ≥13 visits were 0.92 (0.82–1.03), 0.50 (0.38–0.66), 0.62 (0.47–0.82), and 0.99 (0.61–1.60), respectively.

Conclusions

Our findings suggest that appropriate prenatal care, in combination with a higher maternal educational level, can produce a protective interaction effect on LBW risk. Reasonable health resource assignment for different social statuses should be taken into account by policy-makers in developing countries.     

Relations among birth condition, maternal condition, and postnatal growth in captive common marmoset monkeys (Callithrix jacchus)

The present study characterizes the relations among maternal condition, litter size, birth condition, and growth in body weight for a population of common marmosets. The subjects of the study were marmosets born into a single colony between 1994 and 2001. Three sets of analyses were conducted to answer the following questions: 1) Is there a relationship between litter size, maternal condition, and birth condition? In the study population, maternal body weight, maternal age, litter size, and birth condition were related in a complex fashion. Birth weight and prenatal long‐bone growth, as reflected in knee–heel length, were both related to maternal age, with older mothers supporting higher prenatal growth. Age and maternal condition appeared to interact as determinants of long‐bone growth, as the combination of older and larger mothers resulted in significantly longer knee–heel lengths in their offspring. 2) Is there a relationship between birth condition or maternal condition and subsequent growth or final adult size? The early growth rate in this population was similar to early growth rates reported for three different marmoset colonies, suggesting that early growth may be relatively inflexible in this species. However, within this population, the variation that did occur in early growth rate was related to birth weight and maternal weight. Later growth and adult weight were related to birth weight and litter size: small twin infants displayed slower later growth rates and were smaller as adults than twins that began life at a higher birth weight, while the birth weight of triplets was not related to adult size. In these marmosets, small infants that were the result of increased litter size differed from small infants whose small birth size resulted from other factors. This reinforces the proposal that the causes of low birth weight will be relevant to the development of the marmoset as a model of prenatal environmental effects. Am. J. Primatol. 62:83–94, 2004. © 2004 Wiley‐Liss, Inc.     

Maternal and neonatal factors influencing premature birth and low birth weight in Australia

This study identified the influences of neonatal and maternal factors on premature birth and low birth weight in New South Wales, Australia. Bivariate and multivariate analyses were used to explore the association of selected neonatal and maternal characteristics with premature birth and low birth weight. The findings of this study showed that premature birth and low birth weight rate significantly varied by infant sex, maternal age, marital status, Aboriginality, parity, maternal smoking behaviour during pregnancy and maternal hypertension. First-born infants, and infants born to mothers aged less than 20 years, or who were single, separated/divorced, Aboriginal or who smoked during the pregnancy, were at increased risk of being premature or of low birth weight. This study also found that risk factors for premature births and low birth weight were similar in both singleton and multiple births. Gestational age was confirmed to be the single most important risk factor for low birth weight. The findings of this study suggest that in order to reduce the incidence of low birth weight and premature births, health improvement strategies should focus on anti-smoking campaigns during pregnancy and other healthcare programmes targeted at the socially disadvantaged populations identified in the study.     

The Role of Prenatal Care and Social Risk Factors in the Relationship between Immigrant Status and Neonatal Morbidity: A Retrospective Cohort Study

Background and Aim

Literature evaluating association between neonatal morbidity and immigrant status presents contradictory results. Poorer compliance with prenatal care and greater social risk factors among immigrants could play roles as major confounding variables, thus explaining contradictions. We examined whether prenatal care and social risk factors are confounding variables in the relationship between immigrant status and neonatal morbidity.

Methods

Retrospective cohort study: 231 pregnant African immigrant women were recruited from 2007–2010 in northern Spain. A Spanish population sample was obtained by simple random sampling at 1:3 ratio. Immigrant status (Spanish, Sub-Saharan and Northern African), prenatal care (Kessner Index adequate, intermediate or inadequate), and social risk factors were treated as independent variables. Low birth weight (LBW < 2500 grams) and preterm birth (< 37 weeks) were collected as neonatal morbidity variables. Crude and adjusted odds ratios (OR) were estimated by unconditional logistic regression with 95% confidence intervals (95% CI).

Results

Positive associations between immigrant women and higher risk of neonatal morbidity were obtained. Crude OR for preterm births in Northern Africans with respect to nonimmigrants was 2.28 (95% CI: 1.04–5.00), and crude OR for LBW was 1.77 (95% CI: 0.74–4.22). However, after adjusting for prenatal care and social risk factors, associations became protective: adjusted OR for preterm birth = 0.42 (95% CI: 0.14–1.32); LBW = 0.48 (95% CI: 0.15–1.52). Poor compliance with prenatal care was the main independent risk factor associated with both preterm birth (adjusted OR inadequate care = 17.05; 95% CI: 3.92–74.24) and LBW (adjusted OR inadequate care = 6.25; 95% CI: 1.28–30.46). Social risk was an important independent risk factor associated with LBW (adjusted OR = 5.42; 95% CI: 1.58–18.62).

Conclusions

Prenatal care and social risk factors were major confounding variables in the relationship between immigrant status and neonatal morbidity.     

Quality of antenatal care and its dose-response relationship with birth weight in a maternal and child health training institute in Bangladesh

Four hundred and sixty-five pregnant women and their newborn babies were studied at a maternal and child health training institute in Dhaka, Bangladesh, between July 2002 and June 2003 with the objective of (1) examining the relationship between birth weight and maternal factors, and, if there was a dose-response relationship between quality of antenatal care and birth weight, (2) predicting the number of antenatal visits required for women with different significant characteristics to reduce the incidence of low-birth-weight babies. The study revealed that 23.2% of the babies were of low birth weight according to the WHO cut-off point of <2500 g. Mean birth weight was 2674.19+/-425.31 g. A low birth weight was more common in younger (<20 years) and older (> or =30 years) mothers, the low-income group and those with little or no education. The mean birth weight of the babies increased with an increase in quality of antenatal care. The babies of the mothers who had 6+ antenatal visits were found to be 727.26 g heavier than those who had 1-3 visits and 325.88 g heavier than those who had 4-5 visits. No significant relationship was found between number of conception, birth-to-conception interval, BMI at first visit, sex of the newborn and birth weight. Further, from multiple regression analysis (stepwise), it was revealed that number of antenatal visits, educational level of the mother and per capita yearly income had independent effects on birth weight after controlling the effect of each variable. Using multiple regression analysis, the estimated number of antenatal visits required to reduce the incidence of low-birth-weight babies for women with no education and below-average per capita income status was 6; the number required for women with no education and above-average per capita income status was 5; and that for women with education and with any category of income status was 4 visits. So there is a need to stratify women according to their income and educational status so that, along with other measures, the required number of antenatal visits can be estimated beforehand to reduce the incidence of low-birth-weight babies.     

Maternal, neonatal and community factors influencing neonatal mortality in Brazil

Child mortality (the mortality of children less than five years old) declined considerably in the developing world in the 1990s, but infant mortality declined less. The reductions in neonatal mortality were not impressive and, as a consequence, there is an increasing percentage of infant deaths in the neonatal period. Any further reduction in child mortality, therefore, requires an understanding of the determinants of neonatal mortality. 209,628 birth and 2581 neonatal death records for the 1998 birth cohort from the city of S?o Paulo, Brazil, were probabilistically matched. Data were from SINASC and SIM, Information Systems on Live Births and Deaths of Brazil. Logistic regression was used to find the association between neonatal mortality and the following risk factors: birth weight, gestational age, Apgar scores at 1 and 5 minutes, delivery mode, plurality, sex, maternal education, maternal age, number of prior losses, prenatal care, race, parity and community development. Infants of older mothers were less likely to die in the neonatal period. Caesarean delivery was not found to be associated with neonatal mortality. Low birth weight, pre-term birth and low Apgar scores were associated with neonatal death. Having a mother who lives in the highest developed community decreased the odds of neonatal death, suggesting that factors not measured in this study are behind such association. This result may also indicate that other factors over and above biological and more proximate factors could affect neonatal death.     

Changes in the association of low birth weight with socioeconomic status in Hawaii: 1970-1990

This study examines rates of low birth weight (LBW) in the state of Hawaii and changes in the association of LBW with socioeconomic status from 1970 to 1990. The analysis is based on aggregate data for census tracts. Rates of low birth weight were calculated for each census tract. Relative socioeconomic scores were calculated from average household income and years of education. The results show that (1) there was a decrease in the rate of low birth weight infants in Hawaii; and (2) that the correlation between socioeconomic status and low birth weight was substantially reduced, though a significant correlation remains. The paper suggests likely ceiling effects, but that the progressive public health policies and expansion of access to primary health care in Hawaii during this period played a major role in reducing the rate of low birth weight infants and in decreasing socioeconomic inequality on this important health indicator.     

Birth Weight in Relation to Leisure Time Physical Activity in Adolescence and Adulthood: Meta-Analysis of Results from 13 Nordic Cohorts

Background

Prenatal life exposures, potentially manifested as altered birth size, may influence the later risk of major chronic diseases through direct biologic effects on disease processes, but also by modifying adult behaviors such as physical activity that may influence later disease risk.

Methods/Principal Findings

We investigated the association between birth weight and leisure time physical activity (LTPA) in 43,482 adolescents and adults from 13 Nordic cohorts. Random effects meta-analyses were performed on categorical estimates from cohort-, age-, sex- and birth weight specific analyses. Birth weight showed a reverse U-shaped association with later LTPA; within the range of normal weight the association was negligible but weights below and above this range were associated with a lower probability of undertaking LTPA. Compared with the reference category (3.26–3.75 kg), the birth weight categories of 1.26–1.75, 1.76–2.25, 2.26–2.75, and 4.76–5.25 kg, had odds ratios of 0.67 (95% confidence interval: 0.47, 0.94), 0.72 (0.59, 0.88), 0.89 (0.79, 0.99), and 0.65 (0.50, 0.86), respectively. The shape and strength of the birth weight-LTPA association was virtually independent of sex, age, gestational age, educational level, concurrent body mass index, and smoking.

Conclusions/Significance

The association between birth weight and undertaking LTPA is very weak within the normal birth weight range, but both low and high birth weights are associated with a lower probability of undertaking LTPA, which hence may be a mediator between prenatal influences and later disease risk.