Certolizumab treatment during late pregnancy in patients with rheumatic diseases: Low drug levels in cord blood but possible risk for maternal infections. A case series of 13 patients

OBJECTIVE Due to reduction of immune-suppressive drugs, patients with rheumatic diseases can experience an increase in disease activity during pregnancy. In such cases, TNF-inhibitors may be prescribed. However, monoclonal antibodies with the Fc moiety are actively transported across the placenta, resulting in therapeutic drug levels in the newborn. As certolizumab (CZP) lacks the Fc moiety, it may bear a lower risk for the child. METHOD We report a case series of thirteen patients (5 with rheumatoid arthritis and 8 with spondyloarthritis) treated with CZP during late pregnancy to control disease activity. RESULT CZP measured in cord blood of eleven infants ranged between undetectable levels and 1μg/mL whereas the median CZP level of maternal plasma was 32.97μg/mL. Three women developed an infection during the third trimester, of whom one had a severe infection and one had an infection that resulted in a pre-term delivery. During the postpartum period, 6 patients remained on CZP while breastfeeding. CZP levels in the breast milk of two breastfeeding patients were undetectable. CONCLUSION The lack of the active transplacental transfer of CZP gives the possibility to treat inflammatory arthritis during late gestation without potential harm to the newborn. However, in pregnant women treated with TNF-inhibitors and prednisone, attention should be given to the increased susceptibility to infections, which might cause prematurity. CZP treatment can be continued while breastfeeding.

Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation.

BACKGROUND Preterm infants having immature lungs often require respiratory support, potentially leading to bronchopulmonary dysplasia (BPD). Conventional BPD rodent models based on mechanical ventilation (MV) present outcome measured at the end of the ventilation period. A reversible intubation and ventilation model in newborn rats recently allowed discovering that different sets of genes modified their expression related to time after MV. In a newborn rat model, the expression profile 48 h after MV was analyzed with gene arrays to detect potentially interesting candidates with an impact on BPD development. METHODS Rat pups were injected P4-5 with 2 mg/kg lipopolysaccharide (LPS). One day later, MV with 21 or 60% oxygen was applied during 6 h. Animals were sacrified 48 h after end of ventilation. Affymetrix gene arrays assessed the total gene expression profile in lung tissue. RESULTS In fully treated animals (LPS + MV + 60% O(2)) vs. controls, 271 genes changed expression significantly. All modified genes could be classified in six pathways: tissue remodeling/wound repair, immune system and inflammatory response, hematopoiesis, vasodilatation, and oxidative stress. Major alterations were found in the MMP and complement system. CONCLUSION MMPs and complement factors play a central role in several of the pathways identified and may represent interesting targets for BPD treatment/prevention.Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in ~30% of preterm infants born less than 30 wk of gestation (1). Its main risk factors include lung immaturity due to preterm delivery, mechanical ventilation (MV), oxygen toxicity, chorioamnionitis, and sepsis. The main feature is an arrest of alveolar and capillary formation (2). Models trying to decipher genes involved in the pathophysiology of BPD are mainly based on MV and oxygen application to young mammals with immature lungs of different species (3). In newborn rodent models, analyses of lung structure and gene and protein expression are performed for practical reasons directly at the end of MV (4,5,6). However, later appearing changes of gene expression might also have an impact on lung development and the evolution towards BPD and cannot be discovered by such models. Recently, we developed a newborn rat model of MV using an atraumatic (orotracheal) intubation technique that allows the weaning of the newborn animal off anesthesia and MV, the extubation to spontaneous breathing, and therefore allows the evaluation of effects of MV after a ventilation-free period of recovery (7). Indeed, applying this concept of atraumatic intubation by direct laryngoscopy, we recently were able to show significant differences between gene expression changes appearing directly after MV compared to those measured after a ventilation-free interval of 48 h. Immediately after MV, inflammation-related genes showed a transitory modified expression, while another set of more structurally related genes changed their expression only after a delay of 2 d (7). Lung structure, analyzed by conventional 2D histology and also by 3D reconstruction using synchrotron x-ray tomographic microscopy revealed, 48 h after end of MV, a reduced complexity of lung architecture compared to the nonventilated rat lungs, similar to the typical findings in BPD. To extend these observations about late gene expression modifications, we performed with a similar model a full gene expression profile of lung tissue 48 h after the end of MV with either room air or 60% oxygen. Essentially, we measured changes in the expression of genes related to the MMPs and complement system which played a role in many of the six identified mostly affected pathways.

Influence of the gestational stage on the clinical course, lesional development and parasite distribution in experimental ovine neosporosis.

Neospora caninum is considered one of the main causes of abortion in cattle, yet recent studies have also emphasised its relevance as an abortifacient in small ruminants. In order to gain deeper insight into the pathogenesis of ovine neosporosis, pregnant ewes were intravenously inoculated with 10(6) tachyzoites of the Nc-Spain7 isolate at days 40, 90 or 120 of gestation. Infection during the first term resulted in the death of all foetuses between days 19 and 21 post-infection, showing mainly necrotic lesions in foetal liver and the highest parasite DNA detection and burden in both placenta and foetal viscera. After infection at day 90, foetal death was also detected in all ewes, although later (34-48 days post-infection). In this group, lesions were mainly inflammatory. Foetal livers showed the lowest frequency of lesions, as well as the lowest parasite detection and burden. All ewes infected at day 120 delivered viable lambs, although 3 out of 9 showed weakness and recumbency. Neospora DNA was detected in all lambs but one, and parasite burden was similar to that observed in day 90 group. Lesions in this group showed more conspicuous infiltration of inflammatory cells and higher frequency in foetal brain and muscle when compared to both previous groups. These results highlight the crucial role that the stage of gestation plays on the course of ovine neosporosis, similar to that reported in bovine neosporosis, and open the doors to consider sheep as a valid model for exogenous transplacental transmission for ruminant neosporosis.

PICADAR: a diagnostic predictive tool for primary ciliary dyskinesia.

Symptoms of primary ciliary dyskinesia (PCD) are nonspecific and guidance on whom to refer for testing is limited. Diagnostic tests for PCD are highly specialised, requiring expensive equipment and experienced PCD scientists. This study aims to develop a practical clinical diagnostic tool to identify patients requiring testing.Patients consecutively referred for testing were studied. Information readily obtained from patient history was correlated with diagnostic outcome. Using logistic regression, the predictive performance of the best model was tested by receiver operating characteristic curve analyses. The model was simplified into a practical tool (PICADAR) and externally validated in a second diagnostic centre.Of 641 referrals with a definitive diagnostic outcome, 75 (12%) were positive. PICADAR applies to patients with persistent wet cough and has seven predictive parameters: full-term gestation, neonatal chest symptoms, neonatal intensive care admittance, chronic rhinitis, ear symptoms, situs inversus and congenital cardiac defect. Sensitivity and specificity of the tool were 0.90 and 0.75 for a cut-off score of 5 points. Area under the curve for the internally and externally validated tool was 0.91 and 0.87, respectively.PICADAR represents a simple diagnostic clinical prediction rule with good accuracy and validity, ready for testing in respiratory centres referring to PCD centres.

Interferon-gamma and interleukin-4 mRNA expression by peripheral blood mononuclear cells from pregnant and non-pregnant cattle seropositive for bovine viral diarrhea virus

The acceptance of the fetal allograft by pregnant women and mice seems to be associated with a shift from a Th 1 dominated to a Th 2 dominated immune response to certain infectious agents. The goal of this study was to examine cytokine expression in peripheral blood mononuclear cells (PBMCs) from cattle immune to bovine viral diarrhea virus (BVDV) to determine whether pregnancy also has an influence on the type of immune response in this species. Forty-six heifers and cows between 14 months and 13 years of age were included in this study. Twenty-four were seropositive and 22 seronegative for BVDV. Eleven of the seropositive animals and 11 of the seronegative animals were in the eighth month of gestation, the remaining animals were virgin heifers. PBMC from these animals were analyzed for Interferon (IFN)-gamma and Interleukin (IL)-4 mRNA expression by real-time RT-PCR after stimulation with a non-cytopathic strain of BVDV. Additionally, an ELISA was performed to measure IFN-gamma in the supernatants of stimulated cell cultures. In BVDV seropositive animals, IFN-gamma mRNA levels were significantly higher than in BVDV seronegative animals and there was a significant positive correlation between the changes in IFN-gamma and IL-4 mRNA expression. There was, however, no significant difference in IFN-gamma and IL-4 mRNA levels between pregnant and non-pregnant animals. These results are inconsistent with BVDV inducing a Th1 or Th2 biased immune response. Furthermore, a shift in the cytokine pattern during bovine pregnancy was not evident.

Family stress, coping, communication, and adaptation in unintended adolescent pregnancy

Objective. This study examines post-crisis family stress, coping, communication, and adaptation using the Double ABC-X Model of Family Adaptation in families with a pregnant or postpartum adolescent living at home. ^ Methods. Ninety-eight pregnant and parenting adolescents between ages 14 and 18 years (Group 1 at 20 or more weeks gestation; Group 2 at delivery and 8 weeks postpartum) and their parent(s) completed instruments congruent with the model to measure family stress, coping, communication, and adaptation. Descriptive family data was obtained. Mother-daughter data was analyzed for differences between subjects and within subjects using paired t-tests. Correlational analysis was used to examine relationships among variables. ^ Results. More than 90% of families were Hispanic. There were no significant differences between mother and daughter mean scores for family stress or communication. Adolescent coping was not significantly correlated to family coping at any interval. Adolescent family adaptation scores were significantly lower than mothers' scores at delivery and 8 weeks postpartum. Mean individual ratings of family variables did not differ significantly between delivery and 8 weeks postpartum. Simultaneous multiple regression analysis showed that stress, coping, and communication significantly influenced adaptation for mothers and daughters at all three intervals. The relative contributions of the three independent variables exhibited different patterns for mothers and daughters. Parent-adolescent communication accounted for most of the variability in adaptation for daughters at all three intervals. Daughters' family stress ratings were significant for adaptability (p = .01) during the pregnancy and for cohesion (p = .03) at delivery. Adolescent coping (p = .03) was significant for cohesion at 8 weeks postpartum. Family stress was a significant influence at all three intervals for mothers' ratings of family adaptation. Parent-adolescent communication was significant for mother's perception of both family cohesion (p < .001) and adaptability (p < .001) at delivery and 8 weeks, but not during pregnancy. ^ Conclusions. Mothers' and daughters' ratings of family processes were similar regarding family stress and communication, but were significantly different for family adaptation. Adolescent coping may not reflect family coping. Family communication is a powerful component in family functioning and may be an important focus for interventions with adolescents and parents. ^

Is Menopause Optimal?

Various theories have been put forward to explain the fact that humans experience menopause while virtually no animals do. This paper aims to investigate one such theory: children provide a savings technology into old age, but as human babies are usually large and have long gestation periods, a substantial risk of death exists for the mother as she bears children. It seems therefore appropriate to impose a stopping rule for fertility. Given an objective (support for old age) and demographics (mortality of mother and children), an optimal age for menopause can be calculated. Using demographic data from populations that have seen little influence from modern medicine, this optimal age is compared to empirical evidence.

Maternal ingestion of radon-222 in drinking water and the absorbed radiation dose to the embryo

Maternal ingestion of high concentrations of radon-222 (Rn-222) in drinking during pregnancy may pose a significant radiation hazard to the developing embryo. The effects of ionizing radiation to the embryo and fetus have been the subject of research, analyses, and the development of a number of radiation dosimetric models for a variety of radionuclides. Currently, essentially all of the biokinetic and dosimetric models that have been developed by national and international radiation protection agencies and organizations recommend calculating the dose to the mother's uterus as a surrogate for estimating the dose to the embryo. Heretofore, the traditional radiation dosimetry models have neither considered the embryo a distinct and rapidly developing entity, the fact that it is implanted in the endometrial layer of the uterus, nor the physiological interchanges that take place between maternal and embryonic cells following the implantation of the blastocyst in the endometrium. The purpose of this research was to propose a new approach and mathematical model for calculating the absorbed radiation dose to the embryo by utilizing a semiclassical treatment of alpha particle decay and subsequent scattering of energy deposition in uterine and embryonic tissue. The new approach and model were compared and contrasted with the currently recommended biokinetic and dosimetric models for estimating the radiation dose to the embryo. The results obtained in this research demonstrate that the estimated absorbed dose for an embryo implanted in the endometrial layer of the uterus during the fifth week of embryonic development is greater than the estimated absorbed dose for an embryo implanted in the uterine muscle on the last day of the eighth week of gestation. This research provides compelling evidence that the recommended methodologies and dosimetric models of the Nuclear Regulatory Commission and International Commission on Radiological Protection employed for calculating the radiation dose to the embryo from maternal intakes of radionuclides, including maternal ingestion of Rn-222 in drinking water would result in an underestimation of dose. ^

The association between maternal use of selective serotonin reuptake inhibitors during pregnancy and adverse pregnancy outcomes

Maternal use of SSRIs for depression and anxiety during pregnancy has increased over the last decade. Recent studies have questioned the safety of these antidepressants when used in during pregnancy. The aim of this project is to assess the associations between maternal SSRI use and GH, SGA, and preterm birth using data from a U.S. population-based study with self-reported exposure information. ^ The study population is comprised of mothers of control infants from the NBDPS, an ongoing, multi-state, population-based case-control study. Mothers were asked about any use of medications during pregnancy, including the dates they started and stopped taking each medication. Maternal GH was self-reported, while gestational age and birth weight were calculated from information on birth certificates or medical records. ^ Our study found that women exposed to SSRIs in the first trimester and beyond had a higher odds of GH compared to unexposed women (aOR=1.96, 95% CI=1.02-3.74). Women who used SSRIs only in the first trimester had no increased odds of GH (aOR=0.77, 95% CI=0.24-2.50). Women who used SSRIs throughout their entire pregnancy had a two-fold increase in the odds of delivering an SGA infant compared to unexposed women (aOR=2.16, 95% CI=1.01-4.62), while women who reported SSRI use only in the first trimester had a decreased odds of delivering an SGA infant (aOR=0.56, 95% CI=0.14-2.34). Finally, both women who used SSRIs in the first trimester only (aOR=1.58, 95% CI=0.71-3.51) and women who used SSRIs in the first trimester and beyond (aOR=1.49, 95% CI=0.76-2.90) had an increased odds of delivering preterm compared to unexposed women. ^ Results from our study suggest that women who use SSRIs in the first trimester and beyond have an increased and significant odds of GH and SGA. An increase in the odds of preterm birth was also observed among women exposed in this period and is consistent with the results of previous studies which had much larger sample sizes. Women who use SSRIs only in the first trimester appear to have no increased odds of GH or SGA, but may have an increased odds of preterm birth. These findings are consistent with previous studies and highlight how exposure to SSRIs at different points in gestation may result in different risks for these outcomes. ^

Obesity during pregnancy on vagal tone, hemoglobin A1c, oxygenation, and perinatal outcomes

Purpose: To examine the effect of obesity and gestational weight gain on heart rate variability (HRV), oxygenation (HbO 2 and SpO2), hemoglobin A1c (HbA1c) and the frequency of pregnancy complications in obese (O) and non-obese (NO) women.^ Design: The study was an observational comparison study with a repeated measures design. ^ Setting: The setting was a low risk prenatal, university clinic located in a large southeastern metropolitan city. ^ Sample: The sample consisted of a volunteer group of 41 pregnant women who were observed at the three time points of 20, 28, and 36 weeks gestation. ^ Analysis: Analysis included general linear modeling with repeated measures to test for group differences with changes over time on vagal response, HbA1c, and oxygenation. Odds ratios were computed to compare the frequency of birth outcomes. ^ Findings: The interaction effect of time between O and NO women on HbO2 was significant. The mean HP, RSA, and HbO2 changed significantly over time within the NO women. The mean HbA 1c increased significantly over time within the O women. Women with excess gestational weight gain had significantly lower heart period than women with weight gain within the IOM recommendations. Obese women were more likely to have Group B streptococcal infections, gestational hypertension, give birth by cesarean or instrument assistance, and have at least one postnatal event. ^ Conclusions: Monitoring HRV, oxygenation, and HbA1c using minimally invasive measures may permit early identification of alterations in autonomic response. Implementation of interventions to promote vagal tone may help to reduce risks for adverse perinatal outcomes related to obesity. Future studies should examine the effect of obesity on the vagal response and perinatal outcomes. ^

The relationship between premature rupture of the membranes and sepsis in preterm neonates

This investigation was designed as a hospital-based, historical cohort study. The objective of the study was to determine the association between premature rupture of the membranes (PROM) and its duration on neonatal sepsis, infection, and mortality. Neonates born alive with gestational ages between 25 and 35 weeks from singleton pregnancies complicated by PROM were selected. Each of the 507 neonates was matched on gestational age, gender, ethnicity, and month of birth with a neonate without the complication of PROM.^ Data were abstracted from deliveries between January 1979 and December 1985 describing the mother's demographics, labor and delivery treatments and complications, the neonate's demographics, infection status, and medical care. The matched pairs analysis reveals a significant increase in risk of neonatal sepsis (RR = 3.5) and neonatal infection (RR = 2.4) among preterm births complicated by PROM, with a PROM exposure contributing an excess 4 to 5 cases of sepsis per 100 infants (RD = 0.04 for infection and RD = 0.05 for sepsis). Generally PROM remains an important risk factor for sepsis and infection when controlling for various other characteristics, and the risk difference remains constant.^ PROM was not significantly associated with neonatal mortality (RR = 1.02). There is an increase in risk difference for mortality associated with PROM among septic and infected infants, but it is not significant.^ A clear increase in risk of sepsis and infection from PROM occurs when durations of PROM are long (more than 48 hours), e.g., for sepsis the RR is 2.42 for short durations and RR is 6.0 for long durations. No such risk with long duration appears for neonatal mortality.^ This study indicates the importance of close observation of neonates with PROM for sepsis and infection so treatment can be initiated early. However, prematurity is the major risk for sepsis and the practice of early delivery to avoid prolonged durations of PROM does not alter the magnitude of risk. The greatest protection against these infection complications was provided when the neonate weighed over 1500 grams or had more than 33 weeks gestation. ^

A case-control study of the risk factors for eclampsia

Objective. To study the risk factors for eclampsia, a rare but significant complication of pregnancy.^ Target population. All deliveries at or after the 20th week of gestation that took place between January 1, 1977 and March 1992, and between January 1990 and April 1992 at two hospitals in Houston, Texas, respectively.^ Study population. Sixty-six confirmed cases of eclampsia, and 2 groups of randomly selected controls: Non-preeclamptic and preeclamptic deliveries matched to cases on hospital and month of delivery on a 1:4 ratio.^ Exclusions. Women with chronic hypertension, gestational epilepsy, a previous history of epilepsy, and convulsions attributed to encephalitis, meningitis, cerebral tumor, and intracerebral bleeding, and women without a definite diagnosis of preeclampsia/eclampsia.^ Results. Eclampsia developed in 0.52-0.93/1000 deliveries. Fifty-six percent of seizures occurred in the antepartum period, 2% as early as 20 weeks of gestation and 39% between 37 and 42 weeks. Twenty-nine percent and 15% occurred in the postpartum and late postpartum periods, respectively, 8% as late as one week postpartum. A different set of risk factors was involved in the development of eclampsia in non-preeclamptic women than in the progression from preeclampsia to eclampsia. Factors involved in the development of eclampsia included, in addition to twin pregnancy and family history of pregnancy-induced hypertension, fewer than 3 prenatal care visits, urinary tract infections, primigravidity, obesity, black ethnicity, diabetes mellitus, and age $\le$20 years. Risk factors involved in the progression from preeclampsia to eclampsia included fewer than 3 of prenatal care visits, and age $\le$20 years. Protective factors were magnesium sulfate administration prior to seizure, history of abortions and longer gestational age. Having less than 3 prenatal care visits and being less than or equal to 20 years of age were predictors of eclampsia, whether of its development or progression from preeclampsia. Once preeclampsia is diagnosed, primigravid, diabetic, black, or obese women and those with urinary tract infections did not appear to exhibit any increased risk for the progression to eclampsia. The administration of magnesium sulfate was especially protective, followed by a positive history of abortions, 3 or more prenatal care visits, and longer gestational age. The protective effect of MgSO$\sb4$ was only slightly diminished when cases were restricted to the 65% who had a diagnosis of preeclampsia. The progression from preeclampsia to eclampsia may be largely preventable through adequate prenatal care and presumably the administration of magnesium sulfate. (Abstract shortened by UMI.) ^

EFFECTS OF TETRAHYDROCANNABINOL ON SEXUAL DIMORPHISM OF RAT LIVER MIXED FUNCTION OXIDASE

Pregnant Sprague-Dawley rats were gavaged with vehicle (olive oil) or 37.5, 75, 150 or 300 mg/kg of (DELTA)('9)-Tetrahydrocannabinol (THC) on days 18 or 19 of gestation. Male offspring as well as a group of hypophysectomized rats (positive control) were sacrificed at 35 days of age, while females and hypophysectomized control were sacrificed at 36 days of age. The sex-differences in ethylmorphine-N-demethylase and aniline hydroxylase liver activities were evaluated.^ Ethylmorphine-N-demethylase activity showed a significant difference between males and females from control and 37.5, 75 and 150 mg/kg THC dosed groups. Female offspring exposed prenatally to 300 mg/kg THC had a significant increase (p < .01) in N-demethylation activity, while their male counterparts had similar enzyme activity to those found in the male groups from control and 37.5 to 150 mg/kg THC dosed. Moreover, the percent increase in the 300 mg/kg THC dosed females was similar to that detected in the hypophysectomized female rats (positive control). As expected no sex difference in aniline hydroxylase activity was detected in control as well as exposed groups, including the 300 mg/kg THC dosed group.^ It is concluded that (DELTA)('9)-Tetrahydrocannabinol administered once by gavage in days 18 or 19 of gestation alters the liver Mixed Function Oxidase (MFO) sexual dimorphism imprinting process of the rat. ^

A COMPARISON OF NEONATAL MORTALITY BETWEEN HOSPITALS WITH LEVEL III NEWBORN INTENSIVE CARE UNITS AND ALL OTHER HOUSTON HOSPITALS

A number of medical and social developments have had an impact on the neonatal mortality over the past ten to 15 years in the United States. The purpose of this study was to examine one of these developments, Newborn Intensive Care Units (NICUs), and evaluate their impact on neonatal mortality in Houston, Texas.^ This study was unique in that it used as its data base matched birth and infant death records from two periods of time: 1958-1960 (before NICUs) and 1974-1976 (after NICUs). The neonatal mortality of single, live infants born to Houston resident mothers was compared for two groups: infants born in hospitals which developed NICUs and infants born in all other Houston hospitals. Neonatal mortality comparisons were made using the following birth-characteristic variables: birthweight, gestation, race, sex, maternal age, legitimacy, birth order and prenatal care.^ The results of the study showed that hospitals which developed NICUs had a higher percentage of their population with high risk characteristics. In spite of this, they had lower neonatal mortality rates in two categories: (1) white 3.5-5.5 pounds birthweight infants, (2) low birthweight infants whose mothers received no prenatal care. Black 3.5-5.5 pounds birthweight infants did equally well in either hospital group. While the differences between the two hospital groups for these categories were not statistically significant at the p < 0.05 level, data from the 1958-1960 period substantiate that a marked change occurred in the 3.5-5.5 pounds birthweight category for those infants born in hospitals which developed NICUs. Early data were not available for prenatal care. These findings support the conclusion that, in Houston, NICUs had some impact on neonatal mortality among moderately underweight infants. ^

THE BACON CHOW STUDY: THE RELATIONSHIP BETWEEN INFECTIOUS ILLNESS AND GROWTH OF INFANTS

Multiple dietary deficiencies and high rates of infectious illness are major health problems leading to malnutrition and limitation of growth of children in developing countries. Longitudinal studies which provide information on illness incidence and growth velocity are needed in order to untangle the complex interrelationship between nutrition, illness and growth. From 1967 to 1973, researchers led by Dr. Bacon Chow of the Johns Hopkins University School of Hygiene undertook a quasi-experimental prospective study in Suilin Township, Taiwan to determine the effects of a nutritional supplement to the diets of pregnant and lactating women on the growth, development and resistance to disease of their offspring. This dissertation presents results from the analysis of infant morbidity and postnatal growth.^ Maternal nutritional supplementation has no apparent effect on the postnatal growth or morbidity of infants. Significant sex differences exist in growth response to illness and in illness susceptibility. Male infants have more diarrhea and upper respiratory illness. Respiratory illness is positively associated with growth rate in weight in the first semester of life. Diarrhea is significantly negatively associated with growth in length in the second semester. Small-for-date infants are more susceptible to illness in general and have a different pattern of growth response than large-for-date infants.^ Principal components analysis of illness data is shown to be an effective technique for making more precise use of ambiguous morbidity data. Multiple regression with component scores is an accurate method for estimating variance in growth rate predicted by indepenent illness variables. A model is advanced in which initial postnatal growth rate determines subsequent susceptibility to nutritional stress and infection. Initial growth rate is a function of prenatal nutrition, but is not significantly affected by maternal supplementation during gestation or lactation. Critical evaluation is made of nutritional supplementation programs which do not afford disease control.^