The effects of prenatal exposure to Ramadan on stature during childhood and adolescence: Evidence from the Indonesian Family Life Survey

Many pregnant Muslim women fast during the Muslim holy month of Ramadan. A number of studies have reported negative life outcomes in adulthood for children who were prenatally exposed to Ramadan. However, other studies document minimal to no impact on neonatal indicators. Using data from the Indonesian Family Life Survey consisting of 45,246 observations of 21,723 children born to 9771 mothers, we contribute to the current discussion on prenatal exposure to Ramadan by examining the effects on stature (height-for-age Z-scores, weight-for-age Z-scores, and body-mass-index-for-age Z-scores: HAZ, WAZ, and BAZ, respectively) from early childhood to late adolescence (0–19 years of age). We introduce an objective mother’s religiosity indicator to improve the intention-to-treat estimations. Children were classified into three groups based on their mother’s religion-religiosity: religious Muslims, less-religious Muslims, and non-Muslims. Using cluster-robust mother fixed-effects, we found negative effects on stature for children born to religious Muslim mothers. The effects were age-dependent and timing-sensitive. For example, children born to religious Muslim mothers were shorter in late adolescence (15–19 years of age) compared to their unexposed siblings if they were prenatally exposed in the first trimester of pregnancy (HAZ difference = −0.105 SD; p-val. <0.05). Interestingly, we found positive effects on stature for exposed less-religious Muslim children that peak in early adolescence (10–14 years of age) and negative effects on stature for exposed non-Muslim children that occur only in early childhood (0–4 years of age). We nuance our discussion of health and socioeconomic factors to explain these surprising results.     

The origins of monetary income inequality: Patience,human capital,and division of labor

We present an explanation about the origins of monetary income inequality when an economically self-sufficient society opens to a market economy. The chain of associations runs from patience, to the accumulation of different forms of human capital, to self-selection into different occupations, and to the division of labor, which contributes to monetary income inequality. In a self-sufficient society, patience is exogenously determined and people rely on folk knowledge as the only form of human capital. With the establishment of schools, patient and impatient people sort themselves out by the type of human capital they begin to accumulate. Impatient people do not acquire folk knowledge because return to schooling takes many years to bear fruit. Schooling opens opportunities in occupations outside the village, whereas folk knowledge enhances employment opportunities that draw on farming or foraging. Self-selection into different occupations with different earnings potential spawns monetary income inequality. To test the explanation, we draw on data from a foraging–farming society in the Bolivian Amazon, the Tsimane'. We collected data during four consecutive quarters in 1999–2000 and a follow-up interview (2004). Data came from 151 adults (age, 16 years or more) from all households (n=48) in two villages with different levels of market exposure. During 1999–2000, impatience was associated with (a) greater folk knowledge and fewer years of schooling, (b) lower likelihood of working in wage labor, and (c) greater likelihood of working in rural subsistence occupations. People who had been patient in 1999–2000 had greater wage earnings and more modern physical assets in 2004.     

Early developmental influences on hepatic organogenesis

The liver is the largest of the body's organs, with the greatest number of functions, playing a central role in coordinating metabolic homeostasis, nutrient processing and detoxification. The fetal liver forms during early gestation in response to a sequential array of distinct biological events, regulated by intrinsically programmed mechanisms and extracellular signals which instruct hepatic cells to either proliferate, differentiate or undergo apoptosis. A vast number of genes are involved in the initiation and control of liver development, many of which are sensitive to nutritional and hormonal regulation in utero. Moreover, liver mass is influenced by the gestational environment. Therefore, during periods of hepatic cell proliferation and differentiation, the developing fetal liver is sensitive to damage from both internal and external sources including teratogens, infection and nutritional deficiencies. For example, fetuses exposed to decreased materno-fetal nutrition during late gestation have a reduced liver mass, and/or perturbed liver function, which includes increased plasma LDL cholesterol and fibrinogen concentrations. These occur in conjunction with other risk factors present in the early stages of cardiovascular disease i.e. decreased glucose tolerance and insulin insensitivity in later life. Taken together, these findings suggest that liver mass, and later function, are essentially set in utero during fetal development - a process that is ultimately regulated by the intrauterine environment.     

Endoscopic creation and repair of fetal cleft lip.

In utero repair of several life-threatening malformations in the human fetus is now a clinical reality, yet fetal surgery still poses significant risks to both the mother and the unborn child. Preterm labor is a major problem and is directly related to the large hysterotomy required for fetal exposure. Endoscopic surgical manipulation of the fetus, through small uterine "ports," solves this problem and may eventually permit fetal intervention for non-life-threatening malformations. In this pilot study we demonstrated the feasibility of performing endoscopic surgery on the fetus in situ. A lip incision was created and repaired using endoscopic microsurgical techniques in midgestation fetal lambs. This represents the first application of this technique for in utero fetal intervention.     

The Effects of Intermittent Fasting during the Month of Ramadan in Chronic Haemodialysis Patients in a Tropical Climate Country

Background

Chronic kidney disease is an emerging problem in the majority Muslim countries. Despite the uncertainties of the risks involved, some Muslim patients undergoing chronic haemodialysis choose to observe intermittent fasting during the month of Ramadan. This study aims to investigate the effect of Ramadan fasting in haemodialysis patients residing in a tropical climate country.

Methods

This prospective cross sectional study recruited Muslim patients on regular haemodialysis from three haemodialysis centres in Kuala Lumpur from 15^th July 2011 to 29^th August 2011. Patients who fasted for any number of days were included (n = 35, 54% female, age 54±11 years). 89% of patients fasted for more than 15 days and 49% were diabetics. Dialysis parameters and blood samples were obtained one week prior to Ramadan and during the last week of Ramadan. The differences in dialysis parameters and biochemical values pre- and end-Ramadan were examined using paired t-test.

Results

Both pre- and post-dialysis weight were significantly decreased during Ramadan fasting compared to the month prior (p = <0.001). There was a significant decrease in the amount of ultrafiltration (p = 0.002). There were no significant differences in dry weight, inter-dialytic weight gain, mean urea reduction ratio or blood pressure measurements comparing pre- and end of Ramadan fasting. There was a significant increase in serum albumin level (p = 0.006) and decrease in serum phosphate level (p = 0.02) at the end of Ramadan.

Conclusion

Ramadan fasting is associated with reduced weight, improved serum albumin and phosphate level in our population of haemodialysis patients. A larger multi-centre study will allow us to understand more about the effects of fasting in this population.     

Depression and labor supply: Evidence from the Netherlands

We estimate the relationship between depression and labor-market outcomes using data from the Longitudinal Internet studies for the Social Sciences (LISS) panel (2008 — 2018) from the Netherlands. The paper provides three main findings. First, depression is not associated with women’s labor market participation, but it is associated with their likelihood of having paid employment (conditional on being in the labor force). Second, depression is associated with men’s labor force participation, likelihood of having paid employment and likelihood of working full time. Third, severity of depression matters. More severe symptoms are associated with more adverse labor-market outcomes. In addition, we examine the mechanism behind the relationship between depression and labor market outcomes. We find that happiness, life satisfaction, and pessimistic beliefs about the future are partially mediating the effects.     

Hormonal regulation of fetal growth

Fetal growth is a complex process depending on the genetics of the fetus, the availability of nutrients and oxygen to the fetus, maternal nutrition and various growth factors and hormones of maternal, fetal and placental origin. Hormones play a central role in regulating fetal growth and development. They act as maturational and nutritional signals in utero and control tissue development and differentiation according to the prevailing environmental conditions in the fetus. The insulin-like growth factor (IGF) system, and IGF-I and IGF-II in particular, plays a critical role in fetal and placental growth throughout gestation. Disruption of the IGF1, IGF2 or IGF1R gene retards fetal growth, whereas disruption of IGF2R or overexpression of IGF2 enhances fetal growth. IGF-I stimulates fetal growth when nutrients are available, thereby ensuring that fetal growth is appropriate for the nutrient supply. The production of IGF-I is particularly sensitive to undernutrition. IGF-II plays a key role in placental growth and nutrient transfer. Several key hormone genes involved in embryonic and fetal growth are imprinted. Disruption of this imprinting causes disorders involving growth defects, such as Beckwith-Wiedemann syndrome, which is associated with fetal overgrowth, or Silver-Russell syndrome, which is associated with intrauterine growth retardation. Optimal fetal growth is essential for perinatal survival and has long-term consequences extending into adulthood. Given the high incidence of intrauterine growth retardation and the high risk of metabolic and cardiovascular complications in later life, further clinical and basic research is needed to develop accurate early diagnosis of aberrant fetal growth and novel therapeutic strategies.     

Early developmental influences on hepatic organogenesis

The liver is the largest of the body''s organs, with the greatest number of functions, playing a central role in coordinating metabolic homeostasis, nutrient processing and detoxification. The fetal liver forms during early gestation in response to a sequential array of distinct biological events, regulated by intrinsically programmed mechanisms and extracellular signals which instruct hepatic cells to either proliferate, differentiate or undergo apoptosis. A vast number of genes are involved in the initiation and control of liver development, many of which are sensitive to nutritional and hormonal regulation in utero. Moreover, liver mass is influenced by the gestational environment. Therefore, during periods of hepatic cell proliferation and differentiation, the developing fetal liver is sensitive to damage from both internal and external sources including teratogens, infection and nutritional deficiencies. For example, fetuses exposed to decreased materno-fetal nutrition during late gestation have a reduced liver mass, and/or perturbed liver function, which includes increased plasma LDL cholesterol and fibrinogen concentrations. These occur in conjunction with other risk factors present in the early stages of cardiovascular disease i.e. decreased glucose tolerance and insulin insensitivity in later life. Taken together, these findings suggest that liver mass, and later function, are essentially set in utero during fetal development—a process that is ultimately regulated by the intrauterine environment.Key Words: liver, development, maternal constraint, nutrition, placental insufficiency, parity, growth factor     

Nutritional status of Ribeirinhos in Brazil and the nutrition transition

Anthropometric and household data (size, composition, economic activity) were collected from a population of Ribeirinhos living in a rural setting in the eastern Amazon. Data are compared to international reference standards and to other Amazonian populations with the goals of increasing our understanding of the Amazon's largest ethnic group and identifying the relationship between changes in subsistence strategies and nutritional status. Data on height, weight, skinfolds, and circumferences were collected from 471 adults and subadults. The population showed a high degree of stunting with an average HAZ below -2.0 for all age groups over 3 years, and 60% of adult men and 70% of adult women were stunted. Wasting was rare. Average skinfold thicknesses and upper-arm muscle area were near or below average but within the normal range compared to the reference standard, indicating adequate energy and protein stores. Thirty-one percent of males and 29% of females were overweight/obese, and the highest average BMIs were found among men and women in their 40s. Adult males who participated in wage labor had higher weights, BMIs, and UMA values, and were more likely to be overweight and obese compared with those who did not work in wage-labor jobs. Children of fathers who worked in wage labor had higher BMI and UMA values, but there was no significant effect on the nutritional status of other adults in these same households. Signs of the nutrition transition were most noticeable among adult males involved in wage labor because of changes in their diet and activity patterns.     

Lead exposure on critical days of fetal life affects fertility in the female mouse

Female mice were exposed to lead in utero by intravenous injection of lead chloride into the mothers at different stages of pregnancy. At a mature age the mice exposed as fetuses (F1 generation) conceived at a normal rate, but the litter size and fetal survival varied significantly. Small litters and increased numbers of fetal deaths were observed in mice exposed to lead on day 8 of intrauterine life. The live fetuses in this group were normal with respect to weight and morphological appearance. Serum levels of estradiol and progesterone, measured on day 17 of pregnancy, did not differ significantly between F1 mice of a control, unexposed group and of the group exposed to lead on day 8 of intrauterine life. Ovarian follicle counts revealed a significantly smaller number of primordial follicles in the latter group. It is suggested that the exposure to lead at a time of early organogenesis caused the observed fertility decrease by interfering with the development of the female germ cells.     

A long-term, controlled-outcome analysis of in utero versus neonatal cleft lip repair using an ovine model.

Successful open repair of a cleft lip in utero has the advantage of scarless wound healing in the fetus. Unfortunately, no long-term outcome studies have been performed to evaluate the efficacy of these repairs. Moreover, no study to date has compared the long-term results of an in utero cleft lip repair to a similar, control-matched, newborn cleft repair. This study was performed to evaluate the 9-month outcome of in utero cleft lip surgery compared with an identical cleft lip repair performed on infant lambs. In utero epithelialized cleft lips were created through an open hysterotomy in sixteen 65-day-old fetal lambs (term = 140 days) using methods described by Longaker et al. Eight of 16 animals underwent subsequent in utero repair of these clefts at 90 days gestational age. The repair of the remaining eight animals was delayed until 1 week postpartum. At 9 months, the animals were analyzed for changes in lip contour and for the degree of scarring by hematoxylin and eosin and Masson's trichrome collagen staining. Two animals in each group died from preterm labor. Of the animals that survived to term, all repaired lips had some degree of abnormality postoperatively. One of six lips repaired in utero dehisced before delivery. Three of six neonatal repairs dehisced in the first postoperative month. In the remaining animals with intact lip repairs, the vertical lip height on the repaired side was an average of 9 to 12 mm shorter than the normal lip in both the in utero and neonatally repaired animals. Phenotypically, the postnatally repaired animals had more lip distortion and visible notching. Histologically, the in utero repair was scarless and the neonatal repairs had scar throughout the entire vertical height of the lip with an associated loss of hair in this region. Maxillary growth was also evaluated. There was no inhibition of maxillary growth in the animals that underwent in utero cleft lip repair. However, in the neonatal repair group, significant maxillary retrusion was evident. Compared with the cleft side of the maxilla, horizontal growth was decreased by 11 percent (p = 0.01). Compared with the intrauterine repair group, there was a 17-percent decrease in horizontal maxillary width (p = 0.01). Straight-line in utero repair of a cleft lip produces a better long-term result in terms of maxillary growth than a similar repair performed postnatally in the ovine model. There was no diminution in maxillary growth in the animals treated in utero. Histologically, in utero repair of clefts was indeed scarless. However, both lip repairs produced lips that were significantly shorter than their contralateral noncleft sides. This degree of lip shortening would require a secondary lip revision, thereby defeating the purpose of performing an intrauterine repair. Comparisons now need to be made between in utero and neonatal repairs using a Millard-type rotation advancement technique before intrauterine treatment can be considered to be more beneficial than our current treatment modalities.     

Neuroblastoma after prenatal exposure to phenytoin: cause and effect?

We evaluated the causality of the association between intrauterine exposure to phenytoin and postnatal neuroblastoma using an in vitro lymphocyte toxicity assay for phenytoin-induced reactions in an unusual sibship. In addition, we investigated intrauterine phenytoin exposure in a case series of infants and children with neuroblastoma diagnosed over 17 years at our center. The response of lymphocytes from our index case with neuroblastoma exposed in utero to phenytoin was within the normal range, whereas the mother and a sibling with fetal hydantoin syndrome (FHS) exhibited an intermediate toxicity. None of the 188 cases of childhood neuroblastoma diagnosed between 1969 and 1988 had been exposed in utero to phenytoin, indicating that, statistically, the drug cannot be associated with neuroblastoma in more than two cases with this malignancy in our cohort, or in 1.5% of all cases of neuroblastoma. Although our data do not suggest an association between phenytoin in pregnancy and postnatal neuroblastoma, it is still possible that there is an increased risk for neuroblastoma in children with FHS.     

血管紧张素AT1受体抗体阳性孕鼠后代高盐饮食后血管功能障碍

血管紧张素AT1受体抗体(AT1-Ab)可损伤胎盘发育,进而导致胎儿宫内生长受限(intrauterine growth restriction,IUGR).根据胎儿源性成人疾病学说,IUGR会明显增加成人后患心血管疾病的几率.本研究旨在观察AT1-Ab阳性孕鼠后代生长至成年后血管功能有无异常.24只雌性Wistar大...     

Exposure in utero to di(n-butyl) phthalate alters the vimentin cytoskeleton of fetal rat Sertoli cells and disrupts Sertoli cell-gonocyte contact

Di(n-butyl) phthalate (DBP) is commonly used in personal care products and as a plasticizer to soften consumer plastic products. Male rats exposed to DBP in utero have malformations of the male reproductive tract and testicular atrophy characterized by degeneration of seminiferous epithelium and decreased sperm production. In the fetal testis, in utero exposure to DBP reportedly resulted in reduced testosterone levels, Leydig cell aggregates, and multinucleated gonocytes (MNG). We investigated whether exposure in utero to DBP affects rat fetal Sertoli cells and compromises interactions between Sertoli and germ cells in the developing testis. Histological examination showed that MNG occurred at low frequency in the normal fetal rat testis. Exposure in utero at the dose level of DBP above estimated environmental or occupational human exposure levels significantly increased the number of these abnormal germ cells. Postnatally, MNG exhibited aberrant mitoses and were detected at the basal lamina. MNG were not apoptotic in the fetal and postnatal rat testes, as indicated by TUNEL. Sertoli cells in DBP-exposed fetal testis had retracted apical processes, altered organization of the vimentin cytoskeleton, and abnormal cell-cell contacts with gonocytes. The effect of DBP on Sertoli cell morphology at the level of light microscopy was reversed after birth and cessation of exposure. Our data indicate that fetal Sertoli cells are targeted by exposure in utero to DBP and suggest that abnormal interactions between Sertoli and germ cells during fetal life play a role in the development of MNG.     

Fetal responses to maternal and intra-amniotic lipopolysaccharide administration in sheep

A link between intrauterine infection and premature labor is widely accepted, yet the fetal inflammatory responses to such infections are not well understood. Our aim was to use a sheep model in which an inflammatory state was induced by lipopolysaccharide (LPS) administration during pregnancy to the maternal systemic, intra-amniotic or extra-amniotic compartments. Fetal and maternal blood gases and uterine electromyographic activity along with fetal and maternal circulating concentrations of prostaglandins PGE2 and PGFM, cortisol, and interleukin-6 were determined. Maternal systemic LPS treatment resulted in mild maternal hypoxemia, a rise in temperature, greater fetal hypoxemia, and a marked rise in fetal cortisol and PGE2 concentrations that persisted for 48 h. Intra-amniotic administration of LPS at doses higher than those used systemically caused an increase in fetal cortisol and PGE2 concentrations as well as a rise in uterine activity, but these were lesser in magnitude. Extra-amniotic LPS administration caused no overt fetal or maternal inflammatory responses. We conclude that maternal LPS treatment markedly elevated fetal cortisol and PGE2 concentrations. This may be a potential protective mechanism that aids the fetus in the event of premature delivery. The attenuated fetal response to intra-amniotic LPS treatment, despite the much higher dose used, may support a role for the amniotic fluid in protecting the fetus from endotoxin exposure during pregnancy.     

Obesity and the labor market: A fresh look at the weight penalty

This paper applies semiparametric regression models to shed light on the relationship between body weight and labor market outcomes in Germany. We find conclusive evidence that these relationships are poorly described by linear or quadratic OLS specifications. Women's wages and employment probabilities do not follow a linear relationship and are highest at a body weight far below the clinical threshold of obesity. This indicates that looks, rather than health, is the driving force behind the adverse labor market outcomes to which overweight women are subject. Further support is lent to this notion by the fact that wage penalties for overweight and obese women are only observable in white-collar occupations. On the other hand, bigger appears to be better in the case of men, for whom employment prospects increase with weight, albeit with diminishing returns. However, underweight men in blue-collar jobs earn lower wages because they lack the muscular strength required in such occupations.     

2D:4D digit ratio is not a biomarker of developmental programming in baboons (Papio hamadryas species)

We hypothesized second‐to‐fourth hand digit ratio (2D:4D) is a biomarker of developmental programming in 3 baboon groups: intrauterine growth restriction (7 females, 8 males), exposure during fetal life to synthetic glucocorticoids (4 females, 5 males), and controls (66 females, 20 males). 2D:4D was similar between sexes and groups.     

Prior intrauterine position influences body weight in male and female mice

In two longitudinal studies, intrauterine location of male and female Rockland-Swiss mice relative to fetuses of the same and opposite sex dramatically influenced body weight. In one study, body weight of males and females that were located in utero between two female fetuses (OM animals) or between two male fetuses (2M animals) was assessed from birth to the time of weaning (25 days of age). The body weights of 2M females were indistinguishable from those of OM and 2M males on all but a few of the 25 postnatal days of life. Also, 2M females were significantly heavier than OM females from Postnatal Day 6 onward, and 2M males weighed significantly more than OM males from Postnatal Day 19 onward. In a second study, food intake and body weight of animals from different intrauterine locations were examined from 25 to 120 days of age. Regardless of prior intrauterine position, males were always heavier than females. However, prior in utero location modulated body weight in that 2M females were significantly heavier than OM females and 2M males were reliably heavier than OM males. Intrauterine position effects were observed in the absence of any appreciable influence of this variable on levels of food intake. Taken together, the results suggest that prior in utero location may influence metabolic set points involved in the regulation of body weight and fat storage.     

Exposure and fetal growth-associated miRNA alterations in the human placenta

Researchers have begun to examine epigenetic alterations in the placenta, making key advances in understanding the epigenetic regulatory mechanisms of the placenta that define underlying processes of human development and disease. Examining changes in microRNA (miRNA) expression associated with environmental exposures and fetal growth is providing critical insights into the biology of development, response to in utero exposure, and future disease risk assessment. This review aims to highlight previous studies describing changes in miRNA expression in the human placenta associated with in utero exposure and fetal growth and seeks to assess the future directions in this exciting field of research.     

Anabolic effects of insulin and IGF-I in the ovine fetus are reduced by prolonged maternal fasting

Fetal nutritional stress may result in intrauterine growth restriction and postnatal insulin resistance. To determine whether insulin resistance can begin in utero, we subjected late-gestation (130-135 days) ewes to 120 h of complete fasting and compared the results with our previous work in fed ewes (38). We determined the effect of insulin and/or recombinant human (rh)IGF-I infusion on ovine fetal phenylalanine kinetics, protein synthesis, and phenylalanine accretion. Experimental infusates were 1) saline, 2) rhIGF-I plus a replacement dose of insulin (40 nmol IGF-I/h + 16 mIU insulin/h), 3) insulin (890 mIU/h), and 4) IGF-I plus insulin (40 nmol IGF-I/h + 890 mIU insulin/h). During hormone infusion, both glucose and amino acid concentrations were clamped at basal concentrations. Amino acid infusion was required during infusion of either hormone to maintain plasma concentrations constant. However, the amount required during insulin infusion was less than during IGF-I infusion and 40% less than the amount required during identical studies in nonfasted animals. Phenylalanine used for protein synthesis and accretion was increased compared with control animals but again less so than in the nonfasted animals. In contrast to nonfasted animals, neither hormone increased the fractional synthetic rate of skeletal muscle protein nor that of plasma albumin. These results indicate that a short but severe nutritional stress can significantly alter the fetal anabolic response to insulin even when both glucose and amino acid substrate supplies are restored. Therefore, adaptive responses characterized by insulin resistance begin in utero when the fetus is subjected to sufficient nutritional stress.