Annual Pattern of Human Conception in the State of Texas

A total of 2,828,068 State of Texas singleton conceptions, estimated from the date of the first day of the last menstrual period, were assessed for annual periodicity by multiple-component (1-yr fundamental plus the 6- and 3-month harmonics) Cosinor analysis. An annual pattern (p < 0.001) of conception was detected with a December peak, end of July–beginning of August trough and modest amplitude (total peak-to-trough variation) equal to 13.3% of the yearly mean. Annual patterns (p < 0.005) of generally comparable peak and trough times were also documented for conceptions categorized by maternal marital status, age, ethnicity, years of education, birthplace, and county (Texas–Mexico border vs. non-border) of residence. The amplitude, a measure of the prominence of the annual pattern, varied by race (two-fold greater for non-Hispanic Blacks and Hispanics than non-Hispanic Whites), age (50–60% greater for the 19-year-old and younger group than the 20–29 and 30–44-year-old groups) and maternal education (two-fold greater for those with 0–8 than 13 or more years of schooling). Annual patterns (p < 0.001) in conceptions, generally with December peak and end of July–beginning of August trough, were also detected for neonatal variables categorized by birth weight, birth order, gestational age, and gender. The amplitude of the annual pattern in conceptions varied directly with gestational age and inversely with birth weight class.     

Effects of maternal birth season on birth seasonality in the Canadian population during the seventeenth and eighteenth centuries

Birth records of the French-Canadian population for the period 1621-1765 were analyzed retrospectively to examine the effect of maternal birth season on the seasonal distribution of births. Preliminary examination indicated that there was a bimodal pattern in birth seasonality: a major peak in early spring, a trough in early summer, a minor peak in autumn, and a trough around December. Because this seasonality was strongly biased at the level of the first birth by the month of marriage, which was concentrated in November, the seasonality of nonfirst births (n = 32,926) was examined in relation to the four seasons of maternal birth. Mothers born in May-July showed a flatter monthly distribution of nonfirst births at a maternal age of 28 years or more. Analysis of marriage-first birth intervals indicated that mothers who married in August-October showed a lower percentage of immediate conception (intervals of 8-10 months), whereas those mothers born in May-July had a higher percentage of immediate conception. This difference in birth seasonality shown by mothers born in May-July is similar to results from early twentieth-century Japan. Some seasonal infertility factors could have affected the embryos at the earliest stage of pregnancy, modifying a part of the seasonal variation in birth rate.     

Seasonality of births in South-Eastern Nigeria.

A study of seasonal pattern of births in Nigeria was conducted using data on live births for the period 1971-76 from 4 climatically similar southeastern states (Anambra, Imo, Cross River and Rivers State). After pooling the data, the monthly distribution for different years was calculated. The resulting time series was graphically compared with temperature levels during time of conception, or nine months back. Data analysis revealed a seasonal pattern in the monthly distribution of births, with the peak period observed during April-June, and a trough during November-January. Counting 9 months back, the conceptions were calculated as occuring during July, August, or September of the previous year. In terms of the annual agricultural cycle of the southeastern states, July-September corresponded with the period of light farm work or relative idleness for men (main activity during this period is weeding and tending the crops, tasks primarily done by women and children); this is also a period of abundance of fruits, vegetables and palm wine, and rains after dusk, conditions conducive to mating.     

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.     

Sunshine,fertility and racial disparities

This research investigates the effect of sun exposure on fertility, with a special focus on how its effects and consequences for birth outcomes may differ by race. Sun exposure is a key mechanism for obtaining Vitamin D, but this process is inhibited by skin pigmentation. Vitamin D has been linked to male and female fertility and risk of miscarriage, and Vitamin D deficiency is more prevalent among blacks than whites. Using 1989–2004 individual live births data from the Natality Detail Files, county-level, monthly conceptions are estimated as a function of monthly solar insolation, temperature and humidity, as well as month, time and location fixed effects and controls. Insolation has positive, statistically significant effects on fertility for both non-Hispanic blacks and whites, but the effects are stronger and the pattern of effect different for black mothers than white mothers. Poisson estimates from the main model suggest that a 1 kWh increase in average daily insolation in the conception month – approximately the difference in sunshine experienced in the typical September vs. October – increases non-Hispanic black conceptions by 1% and non-Hispanic white conceptions by 0.6%. Allowing insolation's effect to differ by maternal characteristic suggests that the racial differences are not being driven by differences in socioeconomic status (SES). Models that allow for more complicated timing of insolation's effect further suggest that insolation pushes black (white) conceptions into the unfavorable (favorable) season of birth. These estimated effects and our decomposition analyses suggest that insolation – and the implied Vitamin D deficiency underlying its effect–helps explain why black conceptions are more likely to display a seasonal pattern that is disadvantageous to birth outcomes.     

An aetiological study of 290 XXY males,with special reference to the role of paternal age

Summary Data on 290 non-mosaic 47,XXY males have been analysed for possible associations with parental ages at birth, season of birth, sex ratio among sibs, and twinning. Comparison with matched population controls revealed a highly significant association with parental age, which was fully explained by dependence on maternal age and maternal age alone. The maternal age effect was determined with greater precision than in an earlier study of the same material, in which siblings were used as controls, and was estimated to result in an increased risk of between 5% and 10% per annum (p.a.). The estimated independent effect of paternal age, after fitting maternal age, was marginally (but not significantly) negative, and excluded an increased risk in excess of 3% p.a. Paternal age therefore appears to have little if any independent significance in the aetiology of 47,XXY. After correcting for seasonal variations in the population birth rate and smoothing, there was a peak of XXY births in March and a trough in November. Though not statistically significant, the pattern resembled that reported in previous studies, and was similar for both younger and older mothers. The twinning rate for both the XXYs and their sibs, and the sex ratio among the latter, were close to the corresponding population values.     

Photoperiod,temperature, and regional patterns of conceptions in the USA

Twenty-two years of monthly values of birth data for the USA, 1967 through 1988, were analyzed by visual inspection. The data were transformed to remove the influence of length of month and of linear trend, and the values were lagged 9 months to approximate the time of conception. Then, 11-year monthly averages were obtained and plotted as standard scores. Thus two 11-year sets of data were independently analyzed, providing the opportunity of replication. Four distinct temporal patterns were found, differing in month of occurrence of the initial trough and peak and the relative sizes of the two troughs; these characteristics of the temporal pattern change systematically with latitude in the eastern and midwestern states. Data from two other continents, the United Kingdom and Australia, also were analyzed using the same method and found to exhibit a temporal pattern during the year similar to the northern states of the USA. Two biologically relevant variables, temperature and photoperiod, were considered as possible controllers and regulators of the annual rhythmicity. Comparisons of the trends in conceptions with these environmental variables, and inspections of the temperatures and photoperiods at which peaks and troughs in conceptions were found, indicated that these environmental variables could not account for the annual rhythmicity in conceptions.     

Seasonal variation of livebirths, stillbirths, extramarital births and twin maternities in Switzerland.

A study was made of the seasonal variation in all births, and births according to marital status, multiplicity and birth status (live and still) in Switzerland recorded between 1876 and 1990. To obtain seasonal variation in as pure as possible form, our analyses are based on rates. When comparing the seasonality in data sets showing markedly different levels, standardised indices were used. Assuming the length of pregnancies with twins to be about one month shorter than for pregnancies with singletons, lagged twinning rates were calculated but, in comparison with actual twinning rates, the general seasonal variation remained. Therefore, this study was based on actual twinning rates. A monotonic increase in the amplitude of the seasonal variation in general births was noted for the period 1876-1930, with strong seasonal variation holding for 1921-1980. After that, a marked decline in the amplitude can be observed. Seasonality of both all births and twin maternities showed very similar pattern for the periods 1876-1930 and 1969-1990, with maxima in the spring (March-May) and troughs in late autumn (October-December). Twin maternities showed a strong seasonality for the period 1876-1930, being about 20% higher in March than in October. The twinning rate in the period 1876-1930 was about 2.6 per thousand units higher than in the period 1969-90. For twin maternities there was also a stronger seasonal variation during the earlier period than during the later one. The pattern of the seasonal variation for extramarital births, showing a maximum in February (conceptions in May-June) and a minimum in August (conceptions in November-December) with a difference of no less than 24% was more marked than for the marital births. It seems likely that this seasonality of extra-marital maternities was due mainly to seasonal variation of coital rates and multiple ovulation in the early summer months coinciding with optima of light, temperature and food supply. A strong reduction in the rate of stillbirths (gestational age more than 29 weeks) was observed during the twentieth century. The stillbirth rate declined from about 40 per 1000 in the 1870s to fewer than 5 per 1000 in the 1980s. Irrespective of this strong decline in the stillbirth rate, the same seasonal rhythm was noticed throughout the period with high stillbirth rates among births around March and low rates during the summer and autumn.     

Maturation of the pituitary-thyroid axis during the perinatal period.

To clarify the maturation process of the pituitary-thyroid axis during the perinatal period, thyrotropin (TSH) response to thyrotropin releasing hormone (TRH) and serum thyroid hormone levels were examined in 26 healthy infants of 30 to 40 weeks gestation. A TRH stimulation test was performed on 10 to 20 postnatal days. Basal concentrations of serum thyroxine (T4), free thyroxine (free T4) and triiodothyronine (T3) were positively correlated to gestational age and birth weight (p less than 0.001-0.01). Seven infants of 30 to 35 gestational weeks demonstrated an exaggerated TSH response to TRH (49.7 +/- 6.7 microU/ml versus 22.1 +/- 4.8 microU/ml, p less than 0.001), which was gradually reduced with gestational age and normalized after 37 weeks gestation. A similar decrease in TSH responsiveness to TRH was also observed longitudinally in all of 5 high responders repeatedly examined. There was a negative correlation between basal or peak TSH concentrations and postconceptional age in high responders (r = -0.59 p less than 0.05, r = -0.66 p less than 0.01), whereas in the normal responders TSH response, remained at a constant level during 31 to 43 postconceptional weeks. On the other hand, there was no correlation between basal or peak TSH levels and serum thyroid hormones. These results indicate that (1) maturation of the pituitary-thyroid axis is intrinsically controlled by gestational age rather than by serum thyroid hormone levels, (2) hypersecretion of TSH in preterm infants induces a progressive increase in serum thyroid hormones, and (3) although there is individual variation in the maturation process, the feedback regulation of the pituitary-thyroid axis matures by approximately the 37th gestational week.     

Seasonal variation of births in Greece. Temporal changes and regional differences over a 24-year period

The seasonal variation of birth rates in Greece was studied for the years 1956-1979. The relatively constant pattern of the period 1956-1974 (with peak in January and February) turned abruptly into a new one (peak in May-July) for the following years. Whereas the seasonal variation of the first period could be explained as an effect of sociocultural (religious) factors on the rate of conceptions, no explanation was found for its change or for the new pattern. Regional differences between NW and SE Greece were also studied. Seasonal factors and their changes were almost similar in both regions.     

Contents Volume 34 (2003)

Abstract

Our previous studies indicated that temperature and photoperiod were not involved as temporal variables in effecting the annual changes in human conceptions in the USA. However, temperature still receives attention in the current literature as the important variable in determining the temporal pattern of conceptions. Therefore, we present here a replication of our previous study, involving two additional 11‐year cycles of birth data in the USA, from the interval 1945 thru 1966. The data are transformed to remove linear trends, to remove over‐all mean differences, and to remove differences in amplitude. The data are then clustered into the regional groups determined by the previous study. The replication was obtained when these groups exhibited similar patterns within a 11‐year period and among 11‐year periods. The data from four 11‐year intervals are presented, representing more than 100 million Caucasian births in the USA from 1945 thru 1988. The subtle changes with time are described, and a comparison with a southern hemisphere pattern indicates, along with the other data, that temperature is irrelevant in effecting the annual pattern of changes in conceptions.     

Seasonal variation in onset of myocardial infarction--a 7-year single-center study in Italy

Like many other serious acute cardiovascular and cerebrovascular events, acute myocardial infarction (AMI) shows seasonal variation, being most frequent in the winter. We sought to investigate whether age, gender, and hypertension influence this pattern. We studied 4014 (2259 male and 1755 female) consecutive patients with AMI presenting to St. Anna Hospital of Ferrara, Italy between January 1998 and December 2004. Some 1131 (28.2%) of the AMI occurred in persons <65 yrs of age, and 2883 (71.8%) in those > or =65 yrs of age. AMI was over-represented in males (82% in the <65 yr group vs. 56.6% in the > or =65 yr group (chi2=13.99; p<0.001). Hypertension had been previously documented in 964 (24%) of the cases. There were 691 (17.2%) fatal case outcomes; fatal outcomes were significantly higher among the 3054 normotensive (n=614 or 20.1%) than the 964 hypertensive cases (n=77 or 8%; chi2=74.94, p<0.001). AMIs were most frequent in the winter (n=1076 or 26.8% of all the events) and least in the summer (n=924 or 23.0% of all the events; chi2=12.36, p=0.007). The greatest number of AMIs occurred in December (n=379 or 9.44%), and the lowest number in September (n=293 or 7.3%; chi2=11.1, p=0.001). Inferential chronobiological (Cosinor) analysis identified a significant annual pattern in AMI in those > or =65 yrs of age, with a peak between December and February-January for the total sample (p<0.005), January for the sample of males (p=0.014), February for fatal infarctions (p=0.017), and December for non-fatal infarctions (p=0.006). No such temporal variations were detected in any of these categories in those <65 yrs of age. The annual pattern in AMI was also verified by Cosinor analysis in the following hypertensive subgroups: hypertensive males (n=552: January, p=0.014), non-fatal infarctions in hypertensive patients (n=887: January, p=0.018), and elderly normotensives (n=1556: November, p=0.007).     

Seasonal variation in occurrence of pulmonary embolism: analysis of the database of the Emilia-Romagna region, Italy

Seasonal variation in the occurrence of cardiovascular and cerebrovascular events, including pulmonary embolism (PE), has been reported; however, recent large-scale, population-based studies conducted in the United States did not confirm such seasonality. The aim of this large-scale population study was to determine whether a temporal pattern in the occurrence of PE exists. The analysis considered all consecutive cases of PE in the database of all hospital admissions of the Emilia Romagna region in Italy at the Center for Health Statistics between January 1998 and December 2005. PE cases were first grouped according to season of occurrence, and the data were analyzed by the chi(2) test for goodness of fit. Then, inferential chronobiologic (cosinor and partial Fourier) analysis was applied to monthly data, and the best-fitting curve for the annual variation was derived. The total sample consisted of 19,245 patients (8,143 male, mean age 71.6+/-14.1 yrs; 11,102 female, mean age 76.1+/-13.7 yrs). Of these, 2,484 were <65 yrs, 5,443 were between 65 and 74, and 11,318 were > or = 75 yrs. There were 4,486 (23.3%) fatal-case outcomes. PE occurred least frequently in spring (n=4,442 or 23.1%) and most frequent in winter (n=5,236 or 27.2%, goodness of fit chi(2)=75.75, p<0.001). Similar results were obtained for subgroups formed by gender, age, fatal/non-fatal outcome, presence/absence of major underlying co-morbid conditions, and specific risk factors. Inferential chronobiological analysis identified a significant annual pattern in PE, with the peak between November and December for the total sample of cases (p<0.001), males (p<0.001), females (p=0.002), fatal and non-fatal cases (p<0.001 for both), and subgroups formed by age (<65 yrs, p=0.012; 65-74 yrs, p<0.001; > or = 75 yrs, p=0.012). This pattern was independent of the presence/absence of hypertension (p=0.003 and p<0.001, respectively), pulmonary disease (p<0.001 and p<0.001, respectively), stroke (p<0.001 and p=0.004, respectively), neoplasms (p=0.005 and p=0.001, respectively), heart failure (p=0.022 and p<0.001, respectively), and deep vein thrombosis (p=0.002 and p<0.001, respectively). However, only a non-statistically significant trend was found for subgroups formed by cases of diabetes mellitus, infections, renal failure, and trauma.     

Maturation of spontaneous and agonist-induced uterine contractions in the peripartum mouse uterus.

This study tested the hypothesis that the uterus achieves maximum contractile capabilities before the onset of labor. Basal and agonist-stimulated contractions were assessed in uterine strips on Day 15 or 18 of pregnancy, the day of parturition, or 1 day postpartum (n = 4-13 per group). Spontaneous contractions were evident in all groups (n = 4-13 per gestational group); contraction frequency was greater in peripartum groups than in virgin controls ( approximately 4.6 versus 2.8/200 sec). Peak amplitude was nearly 9-fold higher on Days 15 and 18 and over 30-fold higher in the postpartum and 1 day postpartum groups than in nonpregnant mice. Maximum frequency and peak amplitude were achieved in response to 10(-6) to 10(-8) M oxytocin or arginine vasopressin (OT(max) or AVP(max)). Frequency of contractions in response to OT(max) peaked on Day 18 and then declined. Contraction amplitude increased 5-fold on Day 15, declined on the day of birth (equivalent to nonpregnant level), then rebounded to peak on postpartum Day 1. AVP(max) similarly increased frequency and amplitude of contractions, except that maximum contraction amplitude occurred postpartum. Thus, an endogenous oscillator, residing in the uterus, sustains high basal and agonist-induced contraction frequency during pregnancy. Although acceleration of this pacemaker occurred before term, the data suggest that peripartum increases in contraction amplitude characterize the transition to the powerful synchronous contractions of parturition.     

Gastroschisis, low maternal age, and fetal morbidity outcomes

OBJECTIVE: To determine if the risk for fetal growth inhibition among gastroschisis-afflicted fetuses is heightened among younger gravidas (teen mothers). METHOD: This was a retrospective cohort study on live-born infants with isolated gastroschisis delivered in New York State from 1983 through 1999. We compared infants of mature (>20 years) mothers with those of younger (<20 years) mothers with respect to the following indices of fetal morbidity outcomes: low birth weight and very low birth weight, preterm and very pre-term, and small for gestational age. We used adjusted odds ratios to approximate relative risks. RESULTS: A total of 368 infants with isolated gastroschisis were analyzed. The two groups differed in terms of mean gestational age at delivery [Mean + standard deviation(SD) for infants with gastroschisis born to mature mothers = 37.2 weeks +/- 2.8 versus 36.3 weeks + 3.6 for those of teenage mothers(p = 0.01)], as well as mean birth weight [mean birth weight +/- SD for infants with gastroschisis born to mature mothers = 2562.4 grams +548.8 versus 2367.9 grams +/- 645.2 for those of younger mothers (p = 0.004)]. Infants of teen mothers were about twice as likely to be of low birth weight (OR = 1.70; 95% CI = 1.05-2.77) and about three times as likely to be born very preterm when compared to those of mature mothers (OR = 2.80; 95% Cl = 1.02-8.00). No significant differences were observed with respect to very low birth weight, pre-term and small for gestational age. CONCLUSION: Low maternal age appears to be a risk factor for low birth weight and very preterm birth among gastroschisis-affected fetuses. This information is potentially useful for planning by care providers and in counseling affected parents.     

Very Preterm Infants Failing CPAP Show Signs of Fatigue Immediately after Birth

Objective

To investigate the differences in breathing pattern and effort in infants at birth who failed or succeeded on continuous positive airway pressure (CPAP) during the first 48 hours after birth.

Methods

Respiratory function recordings of 32 preterm infants were reviewed of which 15 infants with a gestational age of 28.6 (0.7) weeks failed CPAP and 17 infants with a GA of 30.1 (0.4) weeks did not fail CPAP. Frequency, duration and tidal volumes (VT) of expiratory holds (EHs), peak inspiratory flows, CPAP-level and FiO₂-levels were analysed.

Results

EH incidence increased <6 minutes after birth and remained stable thereafter. EH peak inspiratory flows and VT were similar between CPAP-fail and CPAP-success infants. At 9-12 minutes, CPAP-fail infants more frequently used smaller VTs, 0-9 ml/kg and required higher peak inspiratory flows. However, CPAP-success infants often used large VTs (>9 ml/kg) with higher peak inspiratory flows than CPAP-fail infants (71.8 ± 15.8 vs. 15.5 ± 5.2 ml/kg.s, p <0.05). CPAP-fail infants required higher FiO₂ (0.31 ± 0.03 vs. 0.21 ± 0.01), higher CPAP pressures (6.62 ± 0.3 vs. 5.67 ± 0.26 cmH₂O) and more positive pressure-delivered breaths (45 ± 12 vs. 19 ± 9%) (p <0.05)

Conclusion

At 9-12 minutes after birth, CPAP-fail infants more commonly used lower VTs and required higher peak inspiratory flow rates while receiving greater respiratory support. VT was less variable and larger VT was infrequently used reflecting early signs of fatigue.     

Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies

Objective To compare the perinatal outcome of singleton and twin pregnancies between natural and assisted conceptions.Design Systematic review of controlled studies published 1985-2002.Studies reviewed 25 studies were included of which 17 had matched and 8 had non-matched controls.Main outcome measures Very preterm birth, preterm birth, very low birth weight, low birth weight, small for gestational age, caesarean section, admission to neonatal intensive care unit, and perinatal mortality.Results For singletons, studies with matched controls indicated a relative risk of 3.27 (95% confidence interval 2.03 to 5.28) for very preterm (< 32 weeks) and 2.04 (1.80 to 2.32) for preterm (< 37 weeks) birth in pregnancies after assisted conception. Relative risks were 3.00 (2.07 to 4.36) for very low birth weight (< 1500 g), 1.70 (1.50 to 1.92) for low birth weight (< 2500 g), 1.40 (1.15 to 1.71) for small for gestational age, 1.54 (1.44 to 1.66) for caesarean section, 1.27 (1.16 to 1.40) for admission to a neonatal intensive care unit, and 1.68 (1.11 to 2.55) for perinatal mortality. Results of the non-matched studies were similar. In matched studies of twin gestations, relative risks were 0.95 (0.78 to 1.15) for very preterm birth, 1.07 (1.02 to 1.13) for preterm birth, 0.89 (0.74 to 1.07) for very low birth weight, 1.03 (0.99 to 1.08) for low birth weight, 1.27 (0.97 to 1.65) for small for gestational age, 1.21 (1.11 to 1.32) for caesarean section, 1.05 (1.01 to 1.09) for admission to a neonatal intensive care unit, and 0.58 (0.44 to 0.77) for perinatal mortality. The non-matched studies mostly showed similar trends.Conclusions Singleton pregnancies from assisted reproduction have a significantly worse perinatal outcome than non-assisted singleton pregnancies, but this is less so for twin pregnancies. In twin pregnancies, perinatal mortality is about 40% lower after assisted compared with natural conception.     

Human birth seasonality: latitudinal gradient and interplay with childhood disease dynamics

More than a century of ecological studies have demonstrated the importance of demography in shaping spatial and temporal variation in population dynamics. Surprisingly, the impact of seasonal recruitment on infectious disease systems has received much less attention. Here, we present data encompassing 78 years of monthly natality in the USA, and reveal pronounced seasonality in birth rates, with geographical and temporal variation in both the peak birth timing and amplitude. The timing of annual birth pulses followed a latitudinal gradient, with northern states exhibiting spring/summer peaks and southern states exhibiting autumn peaks, a pattern we also observed throughout the Northern Hemisphere. Additionally, the amplitude of United States birth seasonality was more than twofold greater in southern states versus those in the north. Next, we examined the dynamical impact of birth seasonality on childhood disease incidence, using a mechanistic model of measles. Birth seasonality was found to have the potential to alter the magnitude and periodicity of epidemics, with the effect dependent on both birth peak timing and amplitude. In a simulation study, we fitted an susceptible-exposed-infected-recovered model to simulated data, and demonstrated that ignoring birth seasonality can bias the estimation of critical epidemiological parameters. Finally, we carried out statistical inference using historical measles incidence data from New York City. Our analyses did not identify the predicted systematic biases in parameter estimates. This may be owing to the well-known frequency-locking between measles epidemics and seasonal transmission rates, or may arise from substantial uncertainty in multiple model parameters and estimation stochasticity.     

Brainstem auditory evoked potentials in the fetal sheep, in utero

We studied brainstem auditory evoked potentials (BAEPs) in 8 fetal sheep in utero, ranging in gestational age from 105 to 142 days gestation (normal term 147 days). We could not elicit BAEPs prior to 117 days of gestation. After this age rapid maturation was seen, with three discernible peaks observed prior to 120 days and five peaks after 120 days. A significant (P less than 0.05) gestational age related fall in peak latencies and interpeak latencies was observed. The rate of stimulus presentation that could be tolerated without significant changes in wavepeak latency or amplitude also increased with advancing gestational age. In older fetuses (greater than 125 days), where a differentiated electrocorticogram (ECOG) was observed, differences were seen in latency and amplitude of several of the BAEP wavepeaks dependent upon the state. In high voltage ECOG states the amplitudes of wave IV and V were significantly (P less than 0.05) greater than in the low voltage ECOG state and the latencies of wave I, II and V were significantly (P less than 0.05) longer in low as compared to high voltage ECOG state. The BAEP, being obtainable over very short periods of time, appears to provide a useful indice of neural maturation for the sheep fetus in utero.     

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 (<32 weeks) and with a birth weight too low for their gestational age (less than −1SDS; SGA) with 75 individuals born preterm but with a birth weight appropriate for their gestational age (greater than −1SDS) and a normal postnatal growth (greater than −1SDS at three months post term; AGA). The SGA individuals were not only lighter at birth, but also had a smaller length (p = 3.3 × 10⁻¹³) and head circumference at birth (p = 4.1 × 10⁻¹³). 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.Key words: SGA, DOHAD, IUGR, DNA methylation, famine, IGF2, LEP, INS, GNASAS