Intergenerational effects of maternal birth season on offspring size in rural Gambia

Environmental conditions experienced in early life can influence an individual's growth and long-term health, and potentially also that of their offspring. However, such developmental effects on intergenerational outcomes have rarely been studied. Here we investigate intergenerational effects of early environment in humans using survey- and clinic-based data from rural Gambia, a population experiencing substantial seasonal stress that influences foetal growth and has long-term effects on first-generation survival. Using Fourier regression to model seasonality, we test whether (i) parental birth season has intergenerational consequences for offspring in utero growth (1982 neonates, born 1976-2009) and (ii) whether such effects have been reduced by improvements to population health in recent decades. Contrary to our predictions, we show effects of maternal birth season on offspring birth weight and head circumference only in recent maternal cohorts born after 1975. Offspring birth weight varied according to maternal birth season from 2.85 to 3.03 kg among women born during 1975-1984 and from 2.84 to 3.41 kg among those born after 1984, but the seasonality effect reversed between these cohorts. These results were not mediated by differences in maternal age or parity. Equivalent patterns were observed for offspring head circumference (statistically significant) and length (not significant), but not for ponderal index. No relationships were found between paternal birth season and offspring neonatal anthropometrics. Our results indicate that even in rural populations living under conditions of relative affluence, brief variation in environmental conditions during maternal early life may exert long-term intergenerational effects on offspring.     

Anogenital distance and umbilical cord testosterone level in newborns in Zaria, Northern Nigeria

The anogenital distance (AGD) is the distance between the anus and the base of the penis in males and anus to fourchette (AF) distance in females and is a sexually dimorphic index that, on average, is twice as great in males as in females, so it is used as an indicator of appropiate masculine development. In this study, the anogenital distance (AGD) and anthropometric measurements such as birth weight, birth length, head circumference and placenta weight of 200 newborns (100 male, 100 female) were taken and umbilical cord serum was assayed for testosterone concentration using Radioimmunoassay (Microwell). Data obtained were analysed using Student t-test and Pearson's Correlation Analysis as applicable. Results revealed that mean total anogenital distance was 22.53±0.70mm, and it was significantly higher in males: 31.11±0.64mm than in females: 13.89±0.26mm and we observed that there was positive correlation between birth weight and AGD in females. In males head circumference correlated positively with AGD. The mean cord testosterone concentration was 2.78±0.30ng/ml in males and 2.09±0.22ng/ml in females and did not have any significant correlation with anogenital distance. It was concluded that AGD of the population studied, though high was not significantly higher than AGD in other parts of the world and umbilical cord testosterone level did not have any significant effect on AGD. Keywords: Anogenital distance, Ethnicity, Umbilical cord testosterone, Anthropometry.     

Nicotine consumption before and during pregnancy affects not only newborn size but also birth modus

The associations between cigarette smoking before and during pregnancy and maternal body size (pre-pregnancy weight status, end of pregnancy weight status, weight gain during pregnancy) and newborn size (birth weight, length, head circumference, arcomial circumference), as well as birth modus, were tested in 7803 single full-term births in Vienna. Nicotine consumption before and during pregnancy was found to be associated with smaller and lighter newborns, although maternal weight status and weight gain during pregnancy was significantly higher in smokers. Furthermore, a higher incidence of Caesarean sections was found in smokers. A reduction in the number of daily smoked cigarettes was associated with a lower percentage of low weight newborns (<2500 g).     

Maternal urinary cadmium concentrations in early pregnancy in relation to prenatal and postpartum size of offspring

BackgroundThe impacts of environmental cadmium (Cd) exposure on birth size parameters including weight, length and head circumference (HC) have been reported in multiple studies. However, little remains known of the impacts of maternal Cd exposure during pregnancy on size during in utero development and during early childhood. The aim of this study was to comprehensively investigate impacts of maternal Cd exposure during pregnancy on the size of offspring in utero (from 24 weeks pregnancy) until six months of age.MethodsPregnant mothers were recruited as part of an ongoing prospective birth cohort study based in Guangdong, China. Maternal urine samples were collected in the first and third trimesters of pregnancy, in which Cd concentrations were measured by inductively couple plasma mass spectrometry (ICPMS). In utero size indicators at 24 and 32 week of gestation, including biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and HC were derived from ultrasound examinations. Anthropometric measures of weight, height and HC at birth and one, three and six months of age were also collected. Associations of size measures at the various time points with maternal urinary Cd concentrations were assessed using linear regression models.ResultsThe median urinary Cd concentration was 1.00 and 0.98 μg/g creatinine in the first and third trimesters respectively. In univariate analysis, increased maternal Cd levels in the first trimester were associated with decreased HC (-0.17 cm/ug/g urinary Cd) at birth, and the association was particularly pronounced among males (-0.30 cm/ug/g urinary Cd). First trimester Cd exposure was also found to be significantly associated with decreased infant weight at three and six months of age among girls (−101 g/ug/g and −97 g/ug/g urinary Cd, respectively). Associations of similar magnitude were observed after adjustment for various maternal factors. No significant associations were observed with infant size measures or with measures of Cd in the third trimester.ConclusionsOur detailed study suggests that the first trimester is particularly critical window of susceptibility to sex-specific effects of Cd on size parameters at birth, with some effects persisting to six months of age. These compelling sex-dependent effects on HC and body weight warrant future studies examining longer-term health effects of pregnancy-related Cd exposures.     

Genotype-phenotype correlation in a series of 167 deletion and non-deletion patients with Prader-Willi syndrome

A total of 167 patients with Prader-Willi syndrome (PWS) was studied at the clinical and molecular level. Diagnosis was confirmed by the PW71 methylation test. Quantitative Southern blot hybridizations with a probe for the small nuclear ribonucleoprotein N were performed to distinguish between patients with a deletion (116 patient or 69.5%) and patients without a deletion (51 patients or 30.5%). These two types of patients differed with respect to the presence of hypopigmentation, which was more frequent in patients with a deletion (52%) than in patients without (23%), and to average birth weight of females and males, which was lower in patients with a deletion than in patients without. Newborns with PWS had a lower birth weight and length at term, but normal head circumference in comparison with a control group. This finding aids the identification of the neonatal phenotype. In addition, our data confirm an increased maternal age in the non-deletion group.     

Impact of perinatal dioxin exposure on infant growth: a cross-sectional and longitudinal studies in dioxin-contaminated areas in Vietnam

Dioxin exposure levels remain elevated in residents living around former US Air Force bases in Vietnam, indicating potential adverse impacts on infant growth. In this study, 210 mother-infant pairs in dioxin-contaminated areas in Vietnam were recruited at the infants' birth and followed up for 4 months. Perinatal dioxin exposure levels were estimated by measurement of polychlorinated dibenzo-p-dioxins/furans toxic equivalent (PCDDs/Fs-TEQ) in breast milk. The infants' size was measured at birth and 1 and 4 months after birth, and neurodevelopment was evaluated using the Bayley Scales III at 4 months of age. Among 4 dioxin groups (<25, 25-50, 50-75, ≥75 percentile of PCDDs/Fs-TEQ), cross-sectional comparisons of body size and neurodevelopment scales and comparisons of longitudinally assessed body size were performed respectively. At birth, head circumference of girls in the ≥75 percentile group was significantly larger than those in the <25 and 50-75 percentile groups. At 4 months of age, the weight and body mass index (BMI) of boys in the ≥75 percentile group were significantly lower than those in the other groups. Increase in weight was significantly lower in the ≥75 percentile group in both sexes from birth to 1 month but only in boys at 1-4 months of age. Estimated marginal mean values in a mixed model of weight and BMI during the first 4 months of life were significantly lower in the ≥75 percentile group in boys. In girls, marginal mean values for head circumference were increased with increase in dioxin levels. Only in boys, cognitive, language, and fine motor scores in the ≥75 percentile group were significantly lower than those in the other groups. These results suggested a considerable impact of perinatal dioxin exposure on infant growth, particularly in boys exposed to dioxins at high level of PCDDs/Fs-TEQ.     

Associations of Maternal Retinal Vasculature with Subsequent Fetal Growth and Birth Size

Objective

We aimed to study the maternal retinal microvasculature at mid-trimester and its relationship with subsequent fetal growth and birth size.

Methods

We recruited 732 pregnant women aged 18-46 years in the first trimester with singleton pregnancies. All had retinal photography and fetal scan performed at 26-28 weeks gestation, and subsequent fetal scan at 32-34 weeks gestation. Infant anthropometric measurements were done at birth. Retinal microvasculature was measured using computer software from the retinal photographs.

Results

In multiple linear regression models, each 10 μm narrowing in maternal retinal arteriolar caliber was associated with decreases of 1.36 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.50 mm and 2.30 mm in infant head circumference and birth length at delivery, respectively. Each standard deviation decrease in maternal retinal arteriolar fractal dimension was associated with decreases of 1.55 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.08 mm and 46.42 g in infant head circumference and birth weight at delivery, respectively.

Conclusions

Narrower retinal arteriolar caliber and a sparser retinal vascular network in mothers, reflecting a suboptimal uteroplacental microvasculature during mid-pregnancy, were associated with poorer fetal growth and birth size.     

Prenatal economic shocks and birth outcomes in UK cohort data

We consider the effects of major prenatal economic shocks experienced by mothers on two indicators of newborn-infant health, birth weight and head circumference, using detailed microdata from the UK ALSPAC survey. Controlling for physiological and socioeconomic factors, an economic shock in the first 18 weeks of gestation lowers birth weight by 40–70 g and head circumference by 2–3 mm. We find evidence of transmission via poorer maternal health due to absolute material deprivation and tobacco and alcohol consumption, but not for the endocrinological effects of increased psychosocial anxiety. The fragile-male hypothesis holds for birth weight but not for head circumference, as predicted by recent theories on gender differences in prenatal development.     

Correlation between birth weight, leptin, zinc and copper levels in maternal and cord blood

Leptin and zinc are involved in the regulation of appetite. Copper is a trace element regulating the functions of several cuproenzymes that are essential for life. To evaluate the relationship between zinc and copper status and the leptin system in humans, we examined whether leptin concentrations in the mother and the newborn correlate with the weight of mother, placenta and newborn. A total of 88 pregnant women at 38-42 weeks' gestation were studied. All infants were categorized as small for gestational age (SGA) (n = 16), average for gestational age (AGA) (n = 59) or large for gestational age (LGA) (n = 13). Leptin, zinc, and copper levels were measured in maternal and cord serum at birth. Maternal BMI and placental weight of the LGA groups were significantly higher than those of the SGA and AGA groups. Cord and maternal leptin levels of the SGA groups were significantly lower than those of the AGA and LGA groups. Maternal serum leptin levels were positively correlated with BMI and maternal zinc levels in all groups. Cord serum leptin levels of all groups were positively correlated with birth weight and placental weight. Birth weight was negatively correlated with maternal and cord copper level of all groups. Umbilical leptin concentrations of SGA newborns correlated with leptin concentrations of their mothers. In all pregnancies, birth weight increases in association with increase in cord leptin level. Our results suggest that maternal zinc but not copper level has an effect on maternal serum leptin levels. The increase in copper level in both maternal and cord blood may contribute to restriction in fetal growth.     

The polymorphism in insulin receptor substrate-1 gene and birth weight in neonates at term

BACKGROUND: The mutation of the IRS-1 gene is one of the genetic risk factors which, it is speculated, is associated with insulin resistance or predisposition to type 2 diabetes. The aim of our study was to evaluate the association between the Gly972Arg polymorphism in the IRS-1 gene and birth weight in newborn children with adequate gestational age. MATERIAL AND METHODS: 100 newborn children with adequate gestational age (38-42 weeks), whose mother had no disorders during pregnancy, were studied. Genomic DNA was extracted from umbilical cord blood leukocytes, and Gly972Arg polymorphism in the IRS-1 gene was genotyped using the PCR-based method. RESULTS: Birth weight was significantly lower in the newborn with the IRS-1 Gly972Arg polymorphism compared with a control group (3161.75 +/- 380.86 g vs. 3427.92 +/- 468.86 g). Body length and head circumference at birth were also lower in the neonates with that polymorphism (54.38 +/- 3.13 cm vs. 52.69 +/- 2.91 cm, and 34.08 +/- 1.47 vs. 33.63 +/- 0.81, respectively). CONCLUSIONS: The results suggest that the Gly972Arg genotype is associated with lower birth weight, body length and head circumference in neonates with adequate gestational age.     

Maternal Cadmium Levels during Pregnancy Associated with Lower Birth Weight in Infants in a North Carolina Cohort

Cadmium (Cd) is a ubiquitous environmental contaminant, a known carcinogen, and understudied as a developmental toxicant. In the present study, we examined the relationships between Cd levels during pregnancy and infant birth outcomes in a prospective pregnancy cohort in Durham, North Carolina. The study participants (n = 1027) had a mean Cd level of 0.46 µg/L with a range of <0.08 to 2.52 µg/L. Multivariable models were used to establish relationships between blood Cd tertiles and fetal growth parameters, namely birth weight, low birth weight, birth weight percentile by gestational age, small for gestational age, pre-term birth, length, and head circumference. In multivariable models, high maternal blood Cd levels (≥0.50 µg/L) during pregnancy were inversely associated with birth weight percentile by gestational age (p = 0.007) and associated with increased odds of infants being born small for gestational age (p<0.001). These observed effects were independent of cotinine-defined smoking status. The results from this study provide further evidence of health risks associated with early life exposure to Cd among a large pregnancy cohort.     

Size-at-birth standards for an urban Canadian population.

By random sampling of all births occurring in Hamilton, Ont. over an 18-month period the percentile distributions of the newborn infants'' weight, length, and head and chest circumferences were determined. The resulting standards may be used in the clinical evaluation of size for gestational age. The smoothed 50th percentile values for newborns of 40 weeks gestational age were as follows for boys and girls respectively: birth weight 3530 and 3355 g, crown-heel length 52.0 and 51.3 cm, head circumference 35.2 and 34.4 cm, and chest circumference 33.4 and 32.8 cm. The mother''s height averaged 160.8 +/- 6.1 cm and her weight before the pregnancy 59.2 +/- 10.5 kg. The prevalence of cigarette smoking during pregnancy was 34.8%.     

Prenatal Exposure to Cadmium,Placental Permeability and Birth Outcomes in Coastal Populations of South Africa

Background

The impact of prenatal exposure to cadmium (Cd) on birth outcomes is an area of concern. This study aimed to assess an impact of prenatal Cd exposure on birth outcomes in distinct coastal populations of South Africa.

Methods

Cadmium was measured in maternal blood (CdB) (n = 641), cord blood and in maternal urine (n = 317). This investigation assessed the associations between CdB (non-transformed) and birth outcomes across the 25^th, 50th, and 75th percentile for birth weight, birth length and head circumference, to test for a linear trend. Associations between natural log-transformed maternal CdB, size at birth and other factors were further evaluated using linear mixed-effects modelling with random intercepts.

Results

The average gestational age in the total sample was 38 weeks; 47% of neonates were female, average birth weight was 3065 g and 11% were of low birth weight (< 2500 g). The geometric mean (GM) of the maternal CdB level was 0.25 μg/L (n = 641; 95% CI, 0.23–0.27). The cord blood Cd level was 0.27 μg/L (n = 317; 95% CI, 0.26–0.29) and urine (creatinine-corrected) Cd level was 0.27 μg/L (n = 318; 95% CI, 0.24–0.29). The CdB cord:maternal ratio in the sub-cohort was 1, suggesting that the placenta offers no protective mechanism to the foetus. An inverse association was found between CdB and the lower birth weight percentile in female neonates only (β = - 0.13, p = 0.047). Mothers who reported eating vine vegetables daily had lower levels of CdB (β = - 0.55, p = 0.025). Maternal smoking was associated with an elevation in natural log-transformed CdB levels in both male and female cohorts.

Discussion

Significant inverse associations between prenatal Cd exposure and birth anthropometry were found in female neonates but not in male neonates, suggesting potential sex differences in the toxico-kinetics and toxico-dynamics of Cd.     

Birth month associations with height,head circumference,and limb lengths among peruvian children

Associations between season of birth and body size, morbidity, and mortality have been widely documented, but it is unclear whether different parts of the body are differentially sensitive, and if such effects persist through childhood. This may be relevant to understanding the relationship between early life environment and body size and proportions. We investigated associations between birth month and anthropometry among rural highland (n = 162) and urban lowland (n = 184) Peruvian children aged 6 months to 8 years. Stature; head‐trunk height; total limb, ulna, tibia, hand, and foot lengths; head circumference; and limb measurements relative to head‐trunk height were converted to internal age‐sex‐specific z scores. Lowland and highland datasets were then analyzed separately for birth month trends using cosinor analysis, as urban conditions likely provide a more consistent environment compared with anticipated seasonal variation in the rural highlands. Among highland children birth month associations were significant most strongly for tibia length, followed by total lower limb length and stature, with a peak among November births. Results were not significant for other measurements or among lowland children. The results suggest a prenatal or early postnatal environmental effect on growth that is more marked in limb lengths than trunk length or head size, and persists across the age range studied. We suggest that the results may reflect seasonal variation in maternal nutrition in the rural highlands, but other hypotheses such as variation in maternal vitamin D levels cannot be excluded. Am J Phys Anthropol 154:115–124, 2014. © 2014 The Authors. American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.     

Understanding the different phases of fetal growth.

Fetal growth was studied in 78 newborns who had serial scans in pregnancy. Weight at birth correlated with growth in the first 2 trimesters but better with the growth between 28 and 32 weeks. The correlations for weight at growth cessation were better than those for weight at birth. Crown-heel length at cessation did not correlate with fetal growth in the first 2 trimesters. Maternal weight increase correlated with fetal weight and crown-heel length but not with head circumference at cessation. Maternal prepregnancy weight correlated with fetal growth between 28 and 32 weeks, but not with fetal growth in the second trimester. A negative correlation was found between estimated duration of growth cessation and relative head circumference at birth.     

Fetal growth and subsequent risk of breast cancer: results from long term follow up of Swedish cohort

ObjectiveTo investigate whether size at birth and rate of fetal growth influence the risk of breast cancer in adulthood.DesignCohort identified from detailed birth records, with 97% follow up.SettingUppsala Academic Hospital, Sweden.Participants5358 singleton females born during 1915-29, alive and traced to the 1960 census.ResultsSize at birth was positively associated with rates of breast cancer in premenopausal women. In women who weighed ⩾4000 g at birth rates of breast cancer were 3.5 times (95% confidence interval 1.3 to 9.3) those in women of similar gestational age who weighed <3000 g at birth. Rates in women in the top fifths of the distributions of birth length and head circumference were 3.4 (1.5 to 7.9) and 4.0 (1.6 to 10.0) times those in the lowest fifths (adjusted for gestational age). The effect of birth weight disappeared after adjustment for birth length or head circumference, whereas the effects of birth length and head circumference remained significant after adjustment for birth weight. For a given size at birth, gestational age was inversely associated with risk (P=0.03 for linear trend). Adjustment for markers of adult risk factors did not affect these findings. Birth size was not associated with rates of breast cancer in postmenopausal women.ConclusionsSize at birth, particularly length and head circumference, is associated with risk of breast cancer in women aged <50 years. Fetal growth rate, as measured by birth size adjusted for gestational age, rather than size at birth may be the aetiologically relevant factor in premenopausal breast cancer.

What is already known on this topic

There is some evidence that birth weight is related to risk of breast cancerThe exact nature of any association and whether it differs at premenopausal and postmenopausal ages is unclearFew studies have examined the effect of other measures of birth size and of gestational age

What this study adds

There are strong positive associations between measures of birth size and rates of breast cancer at premenopausal ages that persisted after adjustment for adult risk factorsFor a given birth size, gestational age was inversely associated with risk, suggesting that the rate of fetal growth may be aetiologically relevant to premenopausal breast cancerThere was no association between birth characteristics and rates of breast cancer at postmenopausal ages     

Effect of parental anthropometric parameters on neonatal birth weight and birth length

Data on 550 healthy pregnant women, 550 healthy fathers and their healthy term neonates born from singleton pregnancies (37(+0) through 41(+6) week) during a one-year period were reviewed. Maternal mean age was 27.7 +/- 9.37 years, mean pregestational weight 64.0 +/- 9.50 kg, mean gestational weight gain 15.4 +/- 4.33 kg, mean height 169.7 +/- 5.81 cm, and mean gestational age 40.1 +/- 0.95 weeks. Paternal mean age was 31.4 +/- 6.22 years, mean weight 84.6 +/- 10.35 kg, and mean height 182.8 +/- 6.84 cm. Mean birth weight was 3,709.8 +/- 500.48 g and 3,562.5 +/- 443.02 g, and mean birth length 51.5 +/- 1.91 cm and 50.7 +/- 1.62 cm in male and female newborns, respectively, yielding a birth weight greater by 147.3 g and birth length by 0.8 cm in the former. Study variables showed statistically significant correlations: maternal age contributed to the significant correlation between maternal weight and parity, maternal pregestational weight, weight at delivery, gestational weight gain and body height correlated significantly with neonatal birth weight and birth length, gestational age correlated significantly with neonatal weight and length (p = 0.01 all), parity had no major impact (p > 0.05). Paternal height and weight correlated significantly with neonatal birth weight and birth length (p = 0.01). Study results pointed to a significant correlation of maternal pregestational weight, gestational weight gain and body height, and of paternal weight and height with the neonate birth weight and birth length.     

Prenatal Exposure to Arsenic and Its Effects on Fetal Development in the General Population of Dalian

To evaluate prenatal exposure to arsenic in the general population and its effects on birth size, we conducted a cross-sectional study in Dalian, China. Arsenic concentration in maternal and cord blood was detected by inductively coupled plasma-mass spectrometry and its effects on birth size were analyzed by multivariate analysis and multiple linear regression analysis. Arsenic concentrations in cord blood were significantly lower than those in maternal blood. A significant positive correlation was shown between maternal and cord blood arsenic concentrations. Maternal arsenic concentration was negatively associated with birth weight, height and chest circumference, and fetal arsenic concentration was negatively associated with head circumference. Our results indicate that arsenic exposure at environmental levels in uterus may pose adverse effects on fetal development.     

DNA methylation of IGF2, GNASAS,INSIGF and LEP and being born small for gestational age

Being born small for gestational age (SGA), a proxy for intrauterine growth restriction (IUGR), and prenatal famine exposure are both associated with a greater risk of metabolic disease. Both associations have been hypothesized to involve epigenetic mechanisms. We investigated whether prenatal growth restriction early in pregnancy was associated with changes in DNA methylation at loci that were previously shown to be sensitive to early gestational famine exposure. We compared 38 individuals born preterm (&lt;32 weeks) and with a birth weight too low for their gestational age (-1SDS) and a normal postnatal growth (>-1SDS at 3 months post term; “AGA”). The SGA individuals were not only lighter at birth, but also had a smaller length (P=3.3x10^-13) and head circumference at birth (P=4.1x10^-13). The DNA methylation levels of IGF2, GNASAS, INSIGF and LEP were 48.5%, 47.5%, 79.4% and 25.7% respectively. This was not significantly different between SGA and AGA individuals. Risk factors for being born SGA, including preeclampsia and maternal smoking, were also not associated with DNA methylation at these loci. Growth restriction early in development is not associated with DNA methylation at loci shown to be affected by prenatal famine exposure. Our and previous results by others indicate that prenatal growth restriction and famine exposure may be associated with different epigenetic changes or non epigenetic mechanisms that may lead to similar later health outcomes.     

Secular trends of sizes at birth in Japanese healthy infants born between 1962 and 1988

Body sizes at birth are important clinical indicators widely used for evaluation of prenatal growth. Japan had significant socioeconomic improvement around the 1960s, and these environmental changes may influence physiologically prenatal growth. Furthermore, in Japan, measurements of size at birth for birth certificates are weight and height. Thus, we can refer to annual data on weight and height, but not on head and chest circumference at birth. In this study we measured the weight, height, and head and chest circumference at birth among 6,563 Japanese singleton healthy infants, annually in 1962 and 1988, and examined secular trends of these anthropometric measurements. The boys consistently exceeded the girls in all four variables. Birth weight and height increased significantly from the 1960s to '70s, but did not differ between the '70s and '80s in both boys and girls. Secular trends of head and chest circumference were different from them. In both boys and girls, head and chest circumference increased significantly from the '60s to the '70s, but decreased significantly from the '70s to the '80s. No difference of head circumference during the '60s and '80s was found, but the difference of chest circumference was found. Size at birth was likely to increase from the '60s to '70s in Japan. These findings suggest that the environmental changes such as socioeconomic improvements influence the prenatal growth.