se as feces ea Same INTERNATIONAL MCH PROJECTS II research to wmprove | health services ‘ for mothers and children eit Se ins arias ere See et cata enor oe U.S. DEPARTMENT OF HEALTH, EDUCATION; AND WELFARE Public Health Service : Health Services Administration Bureau of Community Health Services Rockville, Maryland 20857 Bae tN a kate ai io te CN eg ree Pser PR Te A PO | TT ''BERKELEY \ | LIBRARY | | UNIVERSITY OF \c cAUFORNIA PUBLIC HEALTH LIBRARY ''INTERNATIONAL MCH PROJECTS II research to wmprove health services for mothers and children U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Public Health Service Health Services Administration Bureau of Community Health Services Rockville, Maryland 20857 DHEW Publication No. (HSA) 77—5700 1977 ''MCH RESEARCH PUBLICATIONS = //|// C/o The Maternal and Child Health Service Reports on Research To ALON Improve Health Services for Mothers and Children. DHEW Publication No. (HSM) 73-5116 MCH Research Series No. 2: Research To Improve Health Services for Mothers and Children. DHEW Publication No. (HSA) 74-5120 MCH Research Series No. 3: Research To Improve Health Services for Mothers and Children. DHEW Publication No. (HSA) 74-5121 MCH Research Series No. 4: Research To Improve Health Services for Mothers and Children. DHEW Publication No. (HSA) 74-5122 MCH Research Series No. 5: Research To Improve Health Services for Mothers and Children. DHEW Publication No. (HSA) 74-5123 International MCH Projects: Research To Improve Health Services for Mothers and Children. DHEW Publication No. (HSA) 75-5129 Studies in Handicapping Conditions: Research To Improve Health Services for Mothers and Children. DHEW Publication No. (HSA) 75- 5131 Studies in Maternal Health: Research To Improve Health Services for Mothers and Children. DHEW Publication No. (HSA) 75-5132 Studies in Child Health: Research To Improve Health Services for Mothers and Children. DHEW Publication No. (HSA) 76-5133 International MCH Projects—II: Research To Improve Health Services for Mothers and Children. DHEW Publication No. (HSA) 77-5700 il ''FOREWORD Since 1961 the United States Government has supported research projects on maternal and child health in a number of foreign countries. These international projects—all concerned with improving the operation, functioning, and effectiveness of maternal and child health and crippled children’s services—complement the domestic maternal and child health and crippled children’s research program, and their findings have potential application in many programs in the United States. The international research activities have been conducted under the Special Foreign Currency Program, which utilizes U.S.-owned foreign currencies derived from the sale of surplus agricultural commodities as authorized by the Agricultural Trade Development and Assistance Act of 1954 (Public Law 83-480). This is the second publication in the maternal and child health research series to present results of international maternal and child health research projects. The first was entitled “International MCH Projects,” DHEW Publication No. (HSA) 75-5129. Other MCH publications in the series contain summaries of research projects in the United States funded by the Office for Maternal and Child Health of the Bureau of Community Health Services, Health Services Administration. Both the international and domestic research programs were initiated by the Children’s Bureau and later administered by the Maternal and Child Health Service. Because “Patterns of Mortality in Childhood” focuses on one of the major problems in child health, a description of the project is included in this publication. This study was conducted by the Pan American Health Organization, Washington, D.C., under funding by the U.S. State Department’s Agency for International Development. The international research projects have been greatly assisted by U.S. health workers, both governmental and nongovernmental, who volunteered their time to act as project officers and provided technical consultation to the research workers. Much of the credit for this productive international scientific exchange is due to Dr. Katherine Bain, former Chief, International Activities for Maternal and Child Health, whose persistence and ingenuity overcame many obstacles to bring these and other studies to successful completion. The staff that conducted the “Investigation of the Causes of Antenatal Fetal Death” at the General Jewish Hospital, Jerusalem, Israel, acknowledges the guidance and special contributions of the late Winslow T. Tompkins, M.D., obstetrical consultant, Division of Clinical Services, Bureau of Community Health Services. These summaries of research projects were prepared by the Maternal and Child Health Program, School of Public Health, University of California, Berkeley, under MCHS grant MC-R-060208. ili OCT 4 1983 '' ''PROJECTS “ « FIELD STUDY OF CONTROL OF ANEMIA DURING PREGNANCY AND OF TETANUS NEONATORUM IN A RURAL AREA OF PUNJAB, INDIA H. DHILLON, M.D., INDIAN COUNCIL OF MEDICAL RESEARCH, GANGUWAL, PUNJAB, INDIA INVESTIGATION OF THE CAUSES OF ANTENATAL FETAL DEATH 4 MAccaBI SALZBERGER, M.D., and GERTRUDE KALLNER, M.D., GENERAL JEWISH HospITAL, MISGAB LADACH, JERUSALEM, AND ERICH LipaNn, M.D., BEILINSON HosPITAL, PETAH-TIQVA, ISRAEL SEMI-OBJECTIVE METHOD FOR AUDITORY MASS SCREENING OF NEONATES 7 M.M. ALTMAN, M.D., R. SHENHAV, and L. SCHAUDINISCHKY, RAMBAM UNIVERSITY HOSPITAL AND ABA KHousHy MEDICAL SCHOOL, HAIFA, ISRAEL FOLLOWUP STUDIES OF MATURE AND PREMATURE BABIES IN THE UNIVERSITY MATERNITY HOSPITAL IN ALEXANDRIA, EGYPT 10 A.S. ABBASSY, UNIVERSITY OF ALEXANDRIA, EGYPT EARLY DETECTION AND TREATMENT OF PHENYLKETONURIA AND OTHER INBORN ERRORS OF METABOLISM IN POLAND 16 BARBARA CaBALsKA, M.D., and Nina DuczynsKA, PH.D., NATIONAL RESEARCH INSTITUTE FOR MOTHER AND CHILD, WARSAW, POLAND PATTERNS OF MORTALITY IN CHILDHOOD 22 RUTH RICE PUFFER and CarLos V. SERRANO, PAN AMERICAN HEALTH ORGANIZATION, WASHINGTON, D.C. '' ''FIELD STUDY OF CONTROL OF ANEMIA DURING PREGNANCY AND OF TETANUS NEONATORUM IN A RURAL AREA OF PUNJAB, INDIA H. DHILLON, M.D., Indian Council of Medical Research, Ganguwal, Punjab, India, 1971. Project 01-475-2. Between August 1967 and January 1971 the Indian Council of Medical Research studied the feasibility of controlling anemia among pregnant women and tetanus among mothers and infants in rural Punjab, India. Earlier studies in Punjab and other parts of India show that about a quarter of the women in India have hemoglobin levels of less than 10.0 gm percent. In Punjab, about a third of the neonatal deaths are due to tetanus. Twenty-three villages in northeastern Punjab with a combined population of about 20,000 people were selected for the study. Northeast Punjab is a submountainous area with thin, rocky soil. Diet includes rice and corn, but very little protein. Most village wells are contaminated, and the thatched mud houses do not carry piped water. The villages are under the jurisdiction of a primary health center; however, due to limited staff the services of the center did not reach this remote population. The project staff included seven auxiliary nurse-midwives, each responsible for collecting data in an area containing 2,500 to 3,000 people. The nurse-midwives were supervised by two health visitors and a medical officer. A basic health worker assisted the nurse-midwives and was also responsible for malaria control programs and collecting vital statistics. The project also included two laboratory technicians. Tetanus Study The investigation first determined the incidence of neonatal and maternal tetanus in the Punjab area between August 1967 and January 1968. During this preliminary survey there were 56 infant deaths, 12 due to tetanus. There were no deaths of mothers due to tetanus, either during the preliminary survey or the study period—January 1968 through January 1971. During the study period, 50 percent of the pregnant women in the 23 villages received two injections of absorbed tetanus toxoid prepared by the Central Research Institute. Another 10 percent of the expectant mothers had one injection. There was only one infant death due to tetanus during the study period. (The mother of that infant had refused immunization.) Thus, a sequence of two injections for 50 percent of the pregnant women reduced the number of infant deaths due to tetanus from 12 to 1. A program for immunization of children with DPT (diphtheria, pertussis, tetanus) vaccine was also undertaken. Of the 1,754 children immunized, 333 were infants, and 1,421 were toddlers. Only 835 ''children were given all three doses, 385 had two doses, and 530 had one dose. Following the injections, some of the older children developed illnesses such as hyperpyrexia, convulsions, diarrhea, dehydration, and marasmus. The most common symptoms were fever, irritability, and refusal of food. No definitive relationship between the complications and the immunization procedure could be established in a population subject to frequent illnesses without a check of nonimmunized children. Because the villagers were alarmed by these illnesses that they assumed arose from the injections, and because their fears threatened the success of the main study, the campaign of general child immunization was abandoned. On the advice of the advisory council the project policy was changed. Immunization with DPT was given to infants less than 18 months of age. If older children were immunized, they were to be given diphtheria and tetanus vaccines, but not pertussis. For the 326 children immunized after this action, side effects were minimal. Anemia Study Preliminary surveys to determine the hemoglobin level of pregnant women in rural Punjab showed that about half had levels of less than 10 gm percent. The program for treating anemia included screening and treatment for hookworm. When blood tests of pregnant women were taken, their stools were also examined. Of 309 stools examined, 74 percent contained evidence of hookworm. A survey of a single village revealed that between 92 and 98 percent of the adult men and women had hookworm. For the anemia and hookworm program, the 23 villages were randomly placed in four study groups. Women in Group I were placed on antihookworm treatment only; Group II took iron and folic acid twice daily; women in Group III were given a placebo; Group IV had both antihookworm treatment and iron and folic acid. Randomization was done by villages rather than individuals because the project staff thought the women in the small villages would have become hostile to the study if they found out that they were each taking different medicines. Women with a hemoglobin level below 8 gm percent were treated with iron and folic acid for humanitarian reasons no matter which group they belonged to, and were not included in the statistical analysis. Women who took iron and folic acid followed two different regimens. Some took Pernavit—a tablet containing ferrous sulphate, folic acid, vitamin C, and components of the vitamin B complex—twice a day. Others took a Folvite ferrous sulfate tablet twice a day plus a Folvite folic acid tablet twice a day. Alcopar—a granulated powder containing 4.33 grams of bephenium hydroxynapthoate BPC—was administered for treatment of hookworm. ''There were three maternal deaths during the study period, August 1967 to January 1971. All were due to severe anemia, one following severe prenatal hemorrhage and two following postpartum hemorrhage. Two of the mothers who died had received no treatment, and the third, who started treatment late in the second trimester, had taken her medicine irregularly. Among the women taking Pernavit daily, the average change in hemoglobin level from the first test until the time of delivery was +0.11, while for the women receiving no treatment or a placebo, the average change was —0.94. This difference was significant at the .01 level. When results were tabulated only for those women who remained in the study from the first or second trimester through delivery who took 85 percent of the pills or who used at least two tubes of antihookworm medicine, the change was even clearer. The results were as follows: Alcopar 71.10 Placebo —0.85 Iron and Folic Acid ooO.22 Pernavit and Alcopar +0.67 For the 15.5 percent of women who started Pernavit in the first trimester and took at least 85 percent of the prescribed drugs, the mean change in hemoglobin count was +1.00. It was +1.29 for those starting in the second trimester and +0.79 for those starting in the third trimester. The mean change in hemoglobin count averaged —0.13 for women who started taking iron and folic acid in the first trimester and +0.13 for those who started in the second trimester. Most women who started taking iron and folic acid in the third trimester showed no change in hemoglobin count. From these data, the investigator concluded: 1. Best results were obtained when antihookworm treatment was combined with treatment for anemia. 2. The earlier the treatment was started, the more effective it was. 3. Pernavit, combining iron, folic acid, and other vitamins, was more effective than iron and folic acid alone. In addition, more women adhered to this regimen, which involved taking only 1 pill twice a day instead of 2 pills twice a day. Discussion The study demonstrated that a single auxiliary nurse-midwife could contact all pregnant women in a population of 2,500 to 3,000 villagers, scattered over 2 or 3 villages within a radius of 1 to 2 miles. It also discovered that male health workers were as well accepted by the villagers as females. The male technician who collected the blood samples was highly effective in persuading men to adopt birth control measures. ''The investigator found that accuracy of records and proper followup varied with the kind of supervision given through administrative channels. The morale of the auxiliary nurse-midwives and their supervisors, the health visitors, was very important. Similarly, the rate of turnover of field workers affected the acceptance of treatment by mothers. To gain the cooperation of the villagers with the research study, the project officer made contact with local leaders. He then arranged open meetings where he explained the objectives and methodology of the project to the villagers. It became clear that the villagers were willing to participate in the research if they were informed and an attempt was made to deal with their health problems. The project therefore sponsored health clinics, special tuberculosis clinics, and a program to eradicate malaria-carrying mosquitoes. INVESTIGATION OF THE CAUSES OF ANTENATAL FETAL DEATH MAccaBI SALZBERGER, M.D., and GERTRUDE KALLNER, M.D., Research Department of the General Jewish Hospital, Misgab Ladach, Jerusalem, and ERICH LIBAN, M.D., J. Casper Department of Pathology, Beilinson Hospital, Petah-Tiqva, Israel, 1971. U.S. DHEW Project No. 06-481-2. In this study, the investigators surveyed the causes of 943 fetal deaths in Israel between April 1967 and February 1971. The study also attempted to determine whether clinical or pathological examination of every fetal death could reduce the high percentage of cases where the cause of death was unknown. About 600 to 700 fetal deaths occur annually in Israel. Of these, about 50 to 60 percent are usually prenatal deaths, and the remaining percentage of the fetuses die during labor. The study defined a “prenatal death” as the death of a fetus in utero, taking place either after 28 weeks of pregnancy and before the onset of labor or after the fetus weighs at least 1,000 grams and before the onset of labor. The study included 22 hospitals throughout Israel that participated at various times. War conditions occasionally reduced the participation of the hospitals so that the 943 fetal deaths represented 36 percent of all prenatal deaths in Israel during the period. Where the results of clinical tests were available in the medical charts for the 943 fetal deaths, the investigators looked for the following conditions: toxemia, diabetes, and ABO or RH incompatibility. A diagnosis of diabetes was established if at least two of the following four criteria were positive: 1. Indication of diabetes in the clinical history. 2. Abnormal glucose tolerance test (GTT) on the third day after delivery. For the evaluation of oral GTT, the criteria of Fajans and Conn were applied. 3. Giant fetus. 4. Pathological findings indicative of diabetes in the placenta or fetus. 4 ''’ Clinical records were studied for indications of abruptio placenta, hydrocephalus, hydramnios, and postmaturity. In the 22 hospitals, the fetuses were examined macroscopically by the pathologists. These findings, together with the placenta and tissue specimens from internal organs, were sent for histological examination to the Department of Pathology of Kaplan Hospital or Beilinson Hospital. Complete data were not available for every case studied. In evaluating the data, correlations between available clinical and pathological findings were attempted. Several of the categories in this study were tabulated for Jews only, since this was the largest single ethnic group in the sample. Some deaths were excluded because fetal death records could not be matched with the correct clinical records of pregnancy. Results 1. Among 783 records of fetal deaths delivered by Jewish mothers, 473 were matched with official death records. Official records showed that 128 of the fetal deaths from unknown causes had clinical records only. Another 106 fetal deaths from unknown causes had had both clinical records and pathological examinations of the fetus. By reexamining all clinical records, the investigators reduced the number of deaths from unknown causes from 128 to 70. For the other 58 cases, a probable cause of death could be inferred from the records. By reexamining clinical and pathological records when both were available, the number of deaths from unknown causes was reduced from 106 to 7, so that probable causes of death could be inferred in 99 cases. 2. The two conditions most frequently associated with death of the fetus were maternal diabetes and toxemia. Diabetes 1. During pregnancy, 23.3 percent of all the Jewish mothers in the sample were given a diabetic glucose tolerance test (GTT). At the time of delivery, 38.8 percent of the mothers appeared to be diabetic or prediabetic. 2. Seventy of the 103 Jewish mothers who had diabetes were 30 years or older; the remaining 33 were younger than 30. Thirty-one mothers 30 or older and 47 mothers under 30 were prediabetic. Thus older mothers tended to have diabetes and younger mothers tended to have prediabetes. This finding was consistent with the theory that prediabetes may develop into diabetes later in life and may be brought on by a particular stress such as pregnancy. 3. Most of the women examined 6 months after delivery did not show an abnormal GTT curve. 4. In this sample, Oriental Jews had the greatest percentage of diabetes (27 percent, compared to 17 percent for the whole sample). Occidental Jews had the highest proportion of prediabetes (24 percent, compared to 16 percent of the whole sample). ''5. Among the Jewish women in this sample, 101 had consanguineous marriages. Among women with consanguineous marriages, 43.8 percent had diabetes or prediabetes, compared to 27.5 percent of the entire Jewish sample. 6. The researchers calculated the specificity of placental diabetes tests compared to GTT curves. Diabetic curves correlated with diabetes in the placenta in 92 percent of the cases. Prediabetic curves corresponded to evidence of diabetes in the placenta in 66 percent of the cases. Toxemia 1. Almost half of those Jewish mothers who had diabetes or prediabetes also had toxemia. 2. Of the 330 women who were given both clinical and pathological examinations, 28 percent showed pathological evidence of toxemia. Forty-eight of the 93 toxemia cases showed toxemia alone, 22 showed toxemia in conjunction with diabetes, 10 showed toxemia with prediabetes, 10 showed retroplacental haematoma (abruptio placentae), and 3 had blood incompatibility. 3. Occidentals showed more toxemia than Orientals; however, information on ethnic origin was scanty and not entirely reliable. 4. Among mothers 30 years or older, 29 percent had toxemia compared to 26 percent of mothers up to 29 years of age. 5. Of the 82 cases with placental pathology of toxemia, 36 showed no clinical indication of the presence of toxemia in pregnancy. Of the 270 cases with “other pathology,” 18 percent had clinical signs of toxemia. 6. Of the 23 cases which showed abruptio placentae, 21 were associated with either definite or suspected toxemia. Eight were associated with diabetes and toxemia together, and one was associated with diabetes alone. Fetal Deaths by Age 1. The incidence of toxemia reached its peak between the 29th and 32nd week of pregnancy and accounted for 42.9 percent of the fetal deaths in that period. Toxemia accounted for only 7.7 percent of the deaths in fetuses that reached 41 weeks or more. Diabetes, on the other hand, accounted for 8.8 percent of the fetal deaths in the 29- to 32-week period of gestation and 46.3 percent of the deaths after 41 weeks. 2. Diabetes and prediabetes together accounted for 36.2 percent of deaths at 29 weeks of gestation, but 79.5 percent after 41 weeks. Toxemia, including toxemia with other associated conditions, decreased from 53.9 percent to 22.9 percent. Blood incompatibility as a cause of death also declined, beginning at 20.9 percent and ending at 12.8 percent. ''Conclusions The investigators concluded that the risk of prenatal fetal death associated with toxemia and blood incompatibility decreased as the fetus grew older. The risk of fetal death associated with diabetes increased with advancing pregnancy. An important finding of the survey was the high proportion of fetal deaths prior to onset of labor associated with maternal diabetes. In analyzing their findings, the investigators noted that combining clinical information with the results of examination of the placenta and fetus reduced the percentage of fetal deaths from unknown causes to about 5 percent. This is a lower percentage than found in any other survey of fetal deaths. The investigators recommended that a routine, simplified screening test be given to every pregnant woman during the sixth month of pregnancy, and every abnormal GTT be corroborated by plasma insulin assay. To obtain better information on the causes of prenatal mortality, the investigators suggested that obstetricians cooperate with pathologists by ordering fetal and placental examinations for every fetal death. Such examinations may enable the pathologist to detect diabetes in cases where it had not been suspected on clinical examination. SEMI-OBJECTIVE METHOD FOR AUDITORY MASS SCREENING OF NEONATES M.M. ALTMAN, M.D., R. SHENHAV, and L. SCHAUDINISCHKY, ENT Department, Rambam University Hospital and Aba Khoushy Medical School, and the Department of Applied Acoustics, Technion, Israel Institute of Technology, Haifa, Israel, 1972. Grant No. 06-482-2. Following the introduction of an auditory screening program for newborns by Downs and Steritt in 1967, many hospitals initiated mass screening programs to detect hearing impairment in newborns. The results of these programs were disappointing since they located only part of the hearing-impaired population. Subsequently, the Joint Committee of Infant Hearing Screening of the United States discouraged mass screening programs as routine procedures. The importance of the early detection of profound hearing loss has been stressed by all workers in the field for many years because it is essential to the successful rehabilitation of the hearing-impaired child. Identification of hearing impairment before infants are old enough to give clearly evident responses necessitates mass screening of all infants. In most countries, the infant population is available for this purpose only in the newborn nursery. ''Pilot Study The object of this pilot study was to develop an instrument that would register graphically the responses of neonates to auditory stimulation. The instrument, called “‘Accelerometer Recording System” (ARS), was developed for mass screening programs in hospitals to detect profound hearing loss in newborns. The main component of the ARS is an accelerometer that responds to vibrations of the crib caused by movements of the infant. Model The ARS described here was the sixth model developed in a series of experiments. A description of each component follows. 1. Sound source: Tape recorder (SONY TC 200) plays prerecorded thermal band noise, amplified by Audio-Amplifier (BELL 2122-B) into loudspeaker (PHILIPS 8”’), which is mounted on an adjustable stand. 2. Cradle: An infant cradle (34 x 60 x 26 cm) is fitted with a “wooden pillow” consisting of a board (26 x 20 cm) supporting the head and shoulders of the infant. The whole cradle is placed on a concrete slab, weighing over 50 kg, supported by a rubber tire. The concrete slab is covered with a polyurethane sheet. The complete structure is placed on a table. 3. Vibration pickup and analyzing system: An accelerometer is attached to the top of the wooden pillow. A preamplifier amplifies the voltage of the response signal. A response signal occurs when the infant makes any movement that creates a vibration in the highly sensitive wooden pillow. Such responses as eyeblink and increased muscular activities are recorded. 4. Recorder: Voltage is registered by the pen-recorder of an electrocardiograph (FUKUDA RS-100-DH). The marker of the pen- recorder notes the stimulus on the paper and is connected with an automatic timer which releases and controls duration of the stimulus. NOTE: Mention of trade names of components used in building the ARS is for information only and does not constitute any official support or endorsement by the U.S. Department of Health, Education, and Welfare. The accelerometer generates a voltage proportional to the acceleration of the vibrations the infant sets up in the wooden pillow. Infants’ responses to auditory stimuli frequently consist of eyeblink only. To record these responses accurately, it was necessary to eliminate the vibrations set up in the cradle by leg movements. This was accomplished by placing the wooden pillow inside the cradle and the cradle itself on a wooden board. The transmission of vibrations from the floor was prevented by a foam rubber pillow under the wooden pillow and a foam rubber mattress between the cradle and the wooden board. The cradle was weighted by an iron disk so that its vibrations did not affect the wooden pillow. ''In its final design, the instrument was not affected by shouting and stamping on the floor close to it. The pulse of sound emitted during the auditory testing did not affect the instrument. However, a paper ball weighing 1.02 gm, dropped on the wooden pillow from a height of 10 cm, affected the graph. Although the instrument was sensitive to vibrations such as eyeblink and muscular contractions, breathing and heartbeats did not show in the recordings, as their acceleration was very low. Testing Precedure The subjects tested were newborns at the Newborn Nursery of the Rambam Hospital, aged 20 to 96 hours, considered healthy by the pediatricians, and with a birthweight between 2,900 and 4,000 gm. Infants were removed from their cribs and placed in the testing cradle. They remained wrapped in diapers, leaving only their heads and upper limbs for observation. They were classified as 1. “‘awake and quiet,” when their eyes were open and they remained quiet after transfer; 2. “deeply asleep” when not aroused by transfer; and 3. in “slight sleep,” when temporarily aroused by transfer. Fretful or crying infants were excluded. Only neonates older than 20 hours were tested, as previous studies had shown a diminished (observed) response rate in younger infants. Two testers were employed: one observed the infant’s response, the other operated the equipment. Sound stimulus was a 1/3 octave noise band with center frequency of 3150 Hz. Sound level was 90 db at ear of infant. Duration of the signal - was 500 msec. Three stimuli or more were presented, with an interval of at least 5 seconds. Results A distinct recording was obtained in all but seven of the 400 newborns tested. There was a definite relationship between the observed strength of the response and the height of the registered curve. Observation of responses showed that a whole or partial body movement was the prominent reponse in 235 trials, and eyeblink in 132 trials. Observation failed to detect a response in 33 cases. The ARS recorded a response in all but 7 infants. In the tested population there were three infants with a known history of hearing impairment among parents or other siblings. For these infants, observations and recordings showed normal responses, however. Investigators observed that tests with the ARS can be carried out by personnel of a newborn nursery after a very short training period. Each test lasts 2 to 3 minutes. Records are easily read by physicians or nurses. ''The findings of the pilot study suggest that the semi-objective ARS testing procedure is more reliable than any other available mass screening method. The investigators recommend a full evaluation of the ARS to assess the rate of positive and negative errors, through initial mass screening of at least 10,000 newborns and followup screening at 2 years of age. Publication M. M. Altman, R. Shenhav, L. Schaudinischky, ““Semi-Objective Method for Auditory Mass Screening of Neonates,” Acta Oto- Laryngologica (Stockholm), 79 (1-2):46-50, Jan-Feb 1975. FOLLOWUP STUDIES OF MATURE AND PREMATURE BABIES IN THE UNIVERSITY MATERNITY HOSPITAL IN ALEXANDRIA, EGYPT A. S. ABBassy, University of Alexandria, Alexandria, Egypt, 1972. Research Grant No. WA-CB Egypt 3. The objective of this study was to determine the developmental norms, birth weight statistics, and growth curves of Egyptian children up to 5 years of age. Prior to this research, no extensive survey had been done on Egyptian infants or children under 5. At the time of this project, (1965-70), the incidence of prematurity was not known. The mortality data in areas of Egypt with health bureaus showed that prematurity was a significant cause of death during the first year of life. However, the investigator suspected that there was a tendency to certify any death in the first 6 months of life as due to prematurity. The specific goals of the study were: 1. To determine the average birth weight and average body measurements of newborn infants in Alexandria University Maternity Hospital and to compare these findings with the standards from other countries. 2. To determine the incidence of premature birth in Alexandria University Maternity Hospital. 3. To study the epidemiological factors that may contribute to etiology of prematurity in the Alexandria University hospital population. 4. To follow the growth and development, morbidity, and mortality of premature infants as compared with full-term (mature) infants during the first 5 years of life. 5. To improve the health supervision of premature and mature newborn infants while in the hospital and after their discharge by providing continuing followup in clinics and home visits. 10 ''The subjects for this study—1,675 premature babies and 13,852 mature babies—came from the population of all newborns in the Alexandria University Maternity Hospital between 1965 and 1970. However, only babies born during the first 6 months of 1967 and the last 6 months of 1968 were selected in those years, due to financial shortages created by the Middle East War. Many families moved and as their children grew older, easy or cheap transportation to the clinic was not accessible. Many mothers did not perceive any value in the periodic observations and would only come in exchange for small presents. Therefore, the number of infants in the sample varied for each year of development and for each measure of development. The majority of the infants came from families belonging to the middle and poor classes. To carry out this study, expectant mothers were interviewed, newborn babies cared for, home visits made, and health and development records kept, especially for families of premature infants. The project established a well-baby clinic where free milk, vitamins, and medicine were dispensed. The study infants were periodically examined there, the mother was educated about hygiene, immunizations were given, and periodic festivals were arranged to offer gifts for children who had been clean and healthy. The examinations took place at intervals of 2 weeks during the first 6 months, monthly until the end of the first year, every 3 months during the second year, and at half-year intervals thereafter. The following measures were recorded: 1. Body weight of infant to nearest 10 grams. 2. Crown-heel length to the nearest centimeter. 3. Head circumference. 4. Chest circumference. 5. Abdominal circumference (measured only at birth). 6. Span (measured with child on his back and upper limbs stretched laterally; from the tip of the middle finger on one side to the same point on the other side, using a tape passed under the body of the child). The following sections summarize the data resulting from these measurements. Mature Infants Body Weight The 13,852 infants in the study who weighed more than 2,500 grams at birth were considered mature. Of these, valid measurements were obtained for 12,388 infants. There were 6,737 male infants (54.5 percent) and 5,651 females (45.6 percent). The mean birth weight of mature infants was 3.38 kg (3.42 kg for males and 3.34 kg for females). The mean birth weight of mature male newborns was significantly higher than that of mature female newborns. The mean birth weight for mature newborns who were products of multiple pregnancies was 2.99 kg. 11 ''Mothers less than 20 years of age had the smallest babies (averaging 3.23 kg) and mothers older than 45 had the heaviest babies (3.63 kg). The correlation of birth weight with maternal age was statistically significant (r=0.2). There was also a progressive increase in birth weight as birth order increased. The investigator noted that while Egyptian women marry early, they frequently use prolonged lactation as a biological contraceptive. This may help to allow the mother’s body to restore itself and to produce heavier babies as the mother’s body matures. Pattern of Growth in Body Weight To study the growth pattern in the neonatal period, investigators selected 125 mature infants who were healthy and had no complications of pregnancy or delivery. The mean weight of these babies dropped in the first 3 days of life by 40 gm per day: thus they lost an average total of 120 gm during the first 3 days, but attained this weight again at about 8 days of age. The greatest increase in weight occurred during the second 15 days of life. Over the first 3 years, the average birth weight of the mature infants doubled at the age of 5.5 months, tripled at the age of about 20 months, and became fourfold at about 36 months. Studies from other countries, based on selected samples, were used for comparison. The mean body weight at birth in the mature Egyptian child was about equal to that of the American child. Both the Egyptian and American mean birth weights were far below the mean birth weights reported from Sweden and the West Indies (Nevis and Anguilla Islands). During the first 3 months of life, the increments in the mean body weight of the Egyptian child were slightly less than those reported for infants in other parts of the world, except for that of the male infant from Anguilla. During the period when infants were 3-6 months old, there was a great difference in weight between children from Egypt and children from industrialized countries. This difference continued to increase until the end of the second year of life. During the third year, the Egyptian child—like the other children from the developing areas—added more weight than the American or Swedish child. While this growth continued in the fourth and fifth years of life, the mean body weight of the Egyptian child at 5 years was still significantly lower than that of the American child and higher than that reported in the other developing areas. The influence of maternal age and birth order on body weight disappeared by the third month of life. The weight of mature children who were born of multiple births was significantly lower than average until the end of the first year of life. The father’s occupation was used in this study as an index of socioeconomic status. Smaller average body weights and body weight increments were observed among infants of low socioeconomic groups than among infants of middle and high classes. The gap between low and middle-to-high classes appeared when the child was about 6 months 12 ''old. The investigator observed that this is the time when breast feeding customarily is stopped or supplemented by other foods. “The introduction of new foods,” he stated, ‘tis commonly unsuccessful.”’ The Egyptian child’s slow growth at this time is probably due to nutritional factors. During the third year, “‘...the child is able to express his hunger and reach for food. It is then the increments in mean body weight exceed those of the European and American child”’. Body Length The mean body length of mature infants, both male and female, at birth was 50.50 cm. Males averaged 50.77 cm, and females 50.18 cm. Throughout the study period the bodies of males who were mature at birth continued to be longer than the bodies of mature females. The Egyptian infants had a mean birth length very close to that reported for American, Lebanese, and urban Swedish newborns. However, the Egyptian children’s length did not increase as much as did that of children in other countries. This lag was more evident in girls than in boys. The norm for Egyptian children was lower than that of Lebanese children at the end of 1.5 years (end of the Lebanese study), urban Swedish children at the end of 3 years (end of the Swedish study), and American children at the end of 5 years. At the same time, after the Egyptian children reached 2 years of age they grew more centimeters per year than American and Swedish children. Body Span The mean body span of 12,234 newborns weighing more than 2,500 gms was 50.35 cm. Males averaged 50.61 cm and females 50.05 cm—a statistically significant difference. Head Circumference The mean head circumference for 11,926 newborn mature infants at birth was 35.26 cm. For male mature newborns, the mean was 35.47 cm while that for females was 35.01; this statistically significant difference remained consistent throughout the intervals up to 5 years of age. Egyptian norms for both males and females were slightly higher than those for the United States and Sweden. Although the mean head - circumference values of Egyptian boys and girls were slightly higher than American averages at birth, the situation was reversed after 1 year. At the end of the third year, Egyptian average head circumferences were equal to those of Americans. A comparison with Swedish children showed a similar pattern. Chest Circumference The mean chest circumference for 11,842 newborns weighing more than 2,500 grams was 33.73 cm. The average measurment for mature male infants was 33.83 cm, while for mature female infants it was 33.60 cm; the difference was statistically significant. 13 ''The mean chest circumferences at birth for Egyptian boys and girls were greater by about 0.5 cm than those of American males and females. However, chest growth of American children during the first year was faster, so that at 12 months of age the mean for American males and females was 47.6 cm and 47.0 cm respectively, while the Egyptian norms were 46.30 cm and 45.24 cm respectively. By the end of the third and fourth years the figures for the two countries were nearly the same. Developmental Progress From birth to 2.5 years of age, Egyptian infants developed, on the average, as described below. Studies could not be performed beyond the age of 3, as special facilities would have been needed. From birth to | month, very few babies could focus on bright light. From | to 2 months, the ability to focus on bright light and to smile appeared. Between 2 and 3 months, the babies could raise their chins when prone, and they acquired coordinated eye movements. From the third to fourth month, they started cooing and holding their heads up without support of neck. From 5 to 6 months the infants recognized their mothers and reached for objects. They also laughed loudly at pleasurable social contact. From 7 to 8 months the babies could sit alone. They began teething and the lower central incisors erupted. Between 8 and 9 months, the infants could crawl, and the upper central incisors appeared. From 10 to 11 months, the children could stand with support. The lower lateral incisors appeared. Between 11 and 12 months, the children began to walk with support and the upper lateral incisors erupted. Between 12 and 13 months the infants were capable of standing unsupported. They started to speak single words and attempted to walk a few steps. From 14 to 15 months the children could walk alone. During this time, both lower and upper first molars appeared. Between 18 and 19 months all canine teeth erupted, from 19 to 20 months the upper second molars appeared, and between 23 and 24 months the second lower molars erupted. By this time the children could control their sphincters, but by day only. Between 28 and 29 months they could control the sphincters both by day and night. The Egyptian norms for two of the above developmental milestones were later than the American norms. Gesell reported that babies could fix on bright light by the age of 1 week and could support their own heads between 3 and 6 months. For the rest of the milestones, Egyptian norms were the same or earlier than figures for American infants. The investigator observed that Egyptian mothers tended to be more excited about motor achievements than mental ones and to remember with more certainty when the motor activities first occurred. There was no significant difference between the sexes in most of the milestones. An exception was the ability to smile and coo, where males were earlier than females. Females were able earlier than males to raise 14 ''the chin when prone, show coordinated eye movement, hold the head without support, and laugh. No difference in achieving developmental milestones was found among socioeconomic groups; the investigator notes, however, that class differences in the sample were not great. Observing that eruption of teeth was slower in Egyptian infants than in American infants, the investigator surmised that this could be due to genetic factors. The teeth of Egyptian infants erupted in approximately the same order as those of infants of other countries and while primary dentition started later, it was complete in Egyptian infants at an age equal to that of Americans. Premature Infants Body Weight of Premature Infants In this study 1,675 infants weighed 2,500 grams or less at birth and were Classified as premature. This was 10.79 percent of all deliveries at the Alexandria University Maternity Hospital during the 5-year period of the study. The incidence of low birth weight (10.79 percent) fell midway between the values reported in studies of Western populations and studies of Oriental and African peoples. Males constituted 49.9 percent of the premature infants; females 50.1 percent. The mean birth weight for all infants in the premature group was 2.15 kg. The incidence of multiple births was 15.48 percent of the premature group compared to 1.8 percent of mature newborns. There was no significant relationship between mean birth weight and maternal age in the premature infants. Pattern of Growth in Body Weight of Premature Infants The mean body weight for premature infants remained significantly lower than that of mature infants throughout the first 5 years of life. The two groups started with a mean body weight difference of 1.23 kg at birth and ended with a mean body weight difference of 1.32 kg at 5 years of age. The deceleration in weight gain observed in mature infants during the 6 to 24 month age period and subsequent acceleration in mean body weight during the third year were not observed in premature infants. Also, the difference in weight between premature males and premature females was not significant. Body Length of Premature Infants The mean body length of premature infants at birth (45.22 cm) was significantly less than that of mature infants and continued this lag up to the age of 3 years. From 3 to 5 years of age, the premature infant group was still shorter, on the average, but the differences were not significant. f 15 ''EARLY DETECTION AND TREATMENT OF PHENYLKETONURIA AND OTHER INBORN ERRORS OF METABOLISM IN POLAND BARBARA CABALSKA, M.D., and NINA DuCZYNSKA, PH.D., National Research Institute for Mother and Child, Warsaw, Poland, 1969. Research Grant WA-CB-5. The purposes of this study. were to obtain an estimate of the incidence of phenylketonuria (PKU) in Poland and to provide early treatment for diagnosed cases. Screening and analysis took place from April 1964 to June 1969 in the Children’s Clinic at the National Research Institute for Mother and Child in Warsaw. The Institute received blood samples from all infants between the ages of 4 and 7 days in 182 newborn wards in Poland. This mass screening program, taking place at the end of 1964 and continuing through 1969, reached 435,792 newborns. The Guthrie bacterial inhibition assay screening test was used. When the infants in the sample were 2 months old their urine was tested with the ferric chloride (FeC1;) urine test. Dietary treatment consisted of substituting Lofenalac (a protein product from Mead Johnson Company), plus a small amount of milk, for all other sources of dietary protein. At least once a month each child’s prescribed diet was reviewed. Every 6 months the children with PKU had detailed physical and psychological examinations. Parents received the results of all examinations and were given instructions about further dietary and educational management. Psychological tests included the Gesell developmental tests, as modified by Brunet and Lezine, for children younger than 2 years of age. After they were 1% years old, the children were given Truman- Merrill tests. Results of the Screening The detection of 62 cases of PKU among 435,792 newborns yielded an estimated incidence of | per 7,000 newborns in Poland. In particular districts, the incidence ranged from zero to 1:3,988 and was not proportional to the number of these performed. In 92.87 percent of the newborns tested, the level of blood phenylalanine did not exceed 2.0 mg percent, and in 7.07 percent of the newborns blood levels ranged from 2.0 to 4.0 mg percent, which was also considered normal. However, .06 percent or 266 newborns had blood phenylalanine levels greater than 4.0 mg percent, an equivocal result necessitating further testing. Of the 266 suspected cases of PKU, 201 infants had normal tests within 1 or 2 months after birth. Further tests (the Berry test, the La Du test, and other urine tests) confirmed that the remaining 65 infants (34 16 ''girls and 31 boys) had PKU. The phenylalanine level was greater than 30 mg percent in 37 cases, 20 to 30 mg percent in 21 cases, and below 20 mg percent in 4 cases. Later challenge examinations excluded the diagnosis of PKU in three children; it was decided that these children had outlasted forms of phenylalanemia. The mean age at which confirmatory tests were performed was 38 days. The newborns selected for screening in this study were tested again with FeC1, at the end of their second month of life. Followup on infants with anomalous outcomes revealed the following abnormalities: Generalized amino-aciduria—88 cases Increased protein excretion—40 cases Increased cystine excretion—7 cases Increased tyrosine excretion—10 cases. Examinations of patients’ families, using the same screening tests, showed that 9 infants (13.8 percent of the sample group) had older siblings with PKU. The screening of 1,061 individuals at institutions for the mentally retarded revealed that 41 children (3.7 percent) had PKU. The researchers noted that other investigators in Poland have obtained figures ranging from 2.7 percent to 4.8 percent. This compares to 1.6 percent in France, 0.6 to 2.0 percent in Scotland, and 0.4 percent in Czechoslovakia. The researchers suggested that since the gene associated with PKU occurs more often in Scandinavian and Northern European countries, Poland’s location at the borderline of Northern Europe may predispose this country to a higher incidence of the disease. Verification of Diagnosis Verification of the diagnosis of phenylketonuria presented considerable difficulty. It was not possible to carry out verifying tests every 3 or 6 months because the children lived in remote places, and parents very often would not permit frequent hospitalization of their children or frequent visits to outpatient clinics. The diagnostic routine varied, therefore, from patient to patient. On the basis of the evaluations possible, the patients were classified in the following four groups: 1. Typical phenylketonuria—34 cases in children over | year of age. Verification of diagnosis in this group was that the patients had considerable amounts of phenylalanine metabolites in their urine after being fed protein. The phenylalanine curves of urine test results in all the “‘enloaded”’ (fed with protein) children showed the maximum increase at 1.5-2.0 hours after feeding, without any subsequent sharp decrease. 2. Atypical phenylketonuria—2 cases. These children did not consistently test positive on the Guthrie and FeC13 tests. However, their blood phenylalanine returned to normal on the special diet and they had a relatively great tolerance for dietary phenylalanine, so the diagnosis was positive. 17 ''3. Phenylalanemia—1 case verified and 1 suspected. The verified case had a very slow increase of blood phenylalanine level and no metabolites in his urine. The suspected case also developed slowly; however, at the age of 2 he had 20 mg percent blood phenylalanine level, was on the special diet, and was still being observed. _ 4. Incomplete verification of the diagnosis—25 cases. These included: a. Children from birth to 1 year old (6 cases). b. Patients diagnosed in the screening program but treated in other centers (2 cases) and a child whose parents took him off the diet at the age of 5 months (1 case). c. Children who died—1 at 3.5 months and 1 at 6 months. d. Children over | year of age whose diagnosis of PKU during newborn screening had never been verified, but who were under very good dietary control (14 cases). Results of Treatment While the children who received treatment were adjusting to the diet prescribed for PKU, the Guthrie test and urinary PPA with FeCl; urine test were performed twice a week. Analysis of the results of these tests showed that the youngest patients and the patients with the highest blood phenylalanine levels required the longest duration of dietary treatment before their blood levels returned to normal. The average days needed for recovery were as follows: Above Below Age 30 mg % 20-30 mg % 20 mg % 2-4 weeks 28.3 days 15.8 days 4+—6 weeks 18.7 days 12.6 days 7 days 6+-8 weeks 17.2 days 13.6 days The figures showed that infants with the lowest phenylalanine levels who started dietary treatment at the age of 6 to 8 weeks had the fastest recovery. Optimal levels of blood phenylalanine were considered those within the range of 3 to 7 mg percent, although children over 1 year were permitted values up to 12 mg percent. The study report gave detailed results of physical examinations at each 6-month interval until the children were 4 years old. Tests of Development Age 6 Months The results of tests when each child was 6 months old showed that somatic and psychometric development was normal. The only abnormality observed was that 20 of 54 children had slight anemia. In 18 ''13 children it was hypochromic and in | it was hyperchromic. Girls were affected by anemia to a far greater extent than boys (15 out of 20 cases were females). Age 1 Year The somatic and psychomotor development of 12-month-old patients was normal, their average height was significantly shorter than the standard for their age group. Thirteen children had slight anemia, equally distributed among males and females. Age 1.5 Years Among 18-month-old patients, somatic development was still normal but there was a slight tendency to height and weight deficiencies among the males. Age 2 Years At the age of 2, children were still developing normally; 5 out of 32 children were slightly anemic. Age 2.5 Years At the age of 2.5 years, girls tended to be overweight by developmental standards, and boys tended to be underweight. Anemia was found in 4 out of 23 children. Biochemical tests showed that the phenylalanine level was significantly higher than the standard for that age group, and the tyrosine level was significantly lower. Age 4 Years Through the age of 4, somatic and mental development continued to be normal despite continued phenylalanine and tyrosine abnormalities registered by laboratory tests. Psychological Tests Psychological tests of infants showed that about 70 percent of the children tested after | month of age met the standard for their age group, and 30 percent were still at the 1-month developmental level even though they were older. At 2 months, almost all of the children tested psychologically below the standard for their age group. After the age of 2 years, the average intelligence quotient for the PKU children was normal. Investigators observed that the low scores in infancy may not be significant, since it is difficult to measure developmental age in infants. No correlation was found between developmental intelligence quotients and the age at which the PKU diet was started. The 19 ''proportion of IQs below 70 points was greatest among the children for whom poor dietary control was maintained. No correlation was found between EEG results and psychomotor development, except for 2 children with pathology of the nervous system, who also had abnormal EEGs. There were no abnormal EEG curves in children over the age of a Blood Tests In all age groups of patients with PKU, the average hemoglobin and hematocrit levels stayed within the low normal range. The greatest differences appeared in the hemoglobin level, which gradually increased in PKU children up to 4 years of age (it stabilized at 2-2.5 years in healthy children). In contrast to healthy children, hemoglobin and hematocrit levels were slightly higher in boys than in girls. As in healthy children, hemoglobin and hematocrit readings were lowest at 6 months. Anemia was observed more frequently in girls (37 cases) than in boys (16 cases), and most cases were found in children less than 18 months old. Blood calcium and phosphorus levels were normal for PKU children in their first 2 years. In the third year of life, phosphorus levels increased significantly above the norm. After the age of 1, higher alkaline phosphatase levels also appeared but the children showed no symptoms that might indicate the causes of these increases. Plasma Protein Plasma protein levels and the proportional ratio of protein fractions were normal within the course of treatment. After age 4, high levels of total plasma protein were observed. Some displacements in globulin fractions in children over | year (decrease of beta and gamma globulins) required further examination. Blood serum tyrosine consistently decreased among patients on the diet. Evaluation of the children’s somatic development indicated that they had a sufficient supply of protein. Blood serum tryptophan did not show any statistically significant differences from the norm. There was no statistically significant correlation between blood serum phenylalanine and urinary phenylalanine excretion. Older children had more urinary excretion in comparison to blood level than younger children. 20 ''Conclusions The Guthrie test proved to be useful as an instrument for mass screening for PKU. Of 435,792 Guthrie tests, only | gave a false negative result, which was later detected with the ferric chloride urine test. The Guthrie test is technically easy, quick, inexpensive, and requires only a small amount of blood. Diagnosis of PKU presented the following problems in this study: 1. No test for PKU in the postnatal period and early infancy is completely accurate, except for a complicated test for enzymatic activity in the liver tissue. 2. Probability of the correct diagnosis depends directly on the blood phenylalanine level. 3. Where the phenylalanine level is between 20 and 30 mg percent, the diagnosis of PKU is questionable and must be verified by other means. 4. In cases where the initial phenylalanine level is below 20 mg percent, the infant probably does not have typical phenylketonuria, and further tests are required. Useful tests include enloading with protein and the phenylalanine tolerance test. The researchers found that the protein loading test was more reliable, especially for cases of typical PKU. For atypical PKU the only alternative appeared to be careful analysis of the results from many tests. The average age at which dietary treatment was started was 38 days. With this method, the period required for normalizing blood phenylalanine levels was 30 days or less. The therapeutic results obtained showed that this procedure did not affect the normal development of patients. Analysis of indexes of protein metabolic pathways showed normal biosynthesis of body proteins. Most of the treated patients (75 percent) showed developmental quotients and intelligence quotients within the normal range of 90 to 100. Another 14 percent had IQs of 80 to 90. Below normal IQs were found in 10 percent of the patients. The investigators suggested that some brain damage may have existed in patients from birth and may not have been due to poor dietetic management. The investigators felt that treatment started within the first 3 months of life did not exert any negative effect on children with PKU, since the IQ values, while low, were still within the normal ranges. In contrast, children who were not screened or brought to the clinic until the age of 11 months or older showed IQs ranging between 15 and 62, with 1 child having an IQ of 106. For those children treated early in life, no statistically significant correlations were observed between IQ and increases or decreases in blood phenylalanine level. The investigators noted that in the first 2 years of life on the diet, the mean phenylalanine levels did not exceed the safe limits of 12 mg percent. Later in the treatment the levels were higher—between 14 and 16 mg percent. They proposed further investigation into the issue of why psychomotor development remains normal in spite of increased phenylalanine levels. 21 ''The minimal duration of dietary treatment in this study was 4 years, except in the cases of 4 children who showed normal psychomotor development. Three children whose parents stopped the dietary treatment within the first 3 years of life had normal development. On the other hand, 3 children whose treatment was temporarily interrupted were retarded. The investigators concluded that the first years of the child’s life were the period when treatment is mandatory. Since this study was completed in 1969, further research has revealed additional data. Out of 944,627 newborns tested, 131 cases of classical PKU and 10 cases of atypical PKU were found for a frequency of classical PKU in Poland of | in 7,200 and atypical PKU of 1 in 94,000. It was found that both mental and physical development of PKU patients was in normal ranges when dietary treatment was continued. However, an evident drop in IQ scores was observed in January 1975 in a group of 24 patients whose dietary treatment had terminated on an average at age 4.5 years. In two-thirds of the group, changes in EEG records from normal to abnormal were observed. Many of these patients, even those with high IQs, had behavior problems and difficulties in school adaptation. As a result of these findings, the period of dietary treatment for PKU patients in the Institute has been extended to the end of the seventh year of life. PATTERNS OF MORTALITY IN CHILDHOOD [Caracteristicas de la Mortalidad en la Ninez] RUTH RICE PUFFER and CARLOS V. SERRANO, Pan American Health Organization, Scientific Publication 262, Washington, D.C., 1973. The Inter-American Investigation of Mortality in Childhood, a collaborative research project carried out between 1968 and 1972 under the direction of the Pan American Health Organization, studied the circumstances surrounding deaths of 35,095 children under 5 years of age. Thirteen of the 15 projects were located in Latin America (Chaco Province and San Juan Province in Argentina; the La Paz-Viacha Project in Bolivia; Recife, Ribeirao Preto, and Sao Paulo in Brazil; the Santiago-Comunas Project in Chile; Cali, Cartagena, and Medellin in Colombia; San Salvador and rural municipios in El] Salvador; the Kingston-St. Andrew Project in Jamaica; and Monterrey in Mexico). Two studies took place in North America, one in California, U.S.A.,; and the other in Quebec Province, Canada. The investigation was supported through a research contract with the U.S. Agency for International Development. 22 ''To make the diagnoses, the investigation used information from hospital and autopsy records and interviews conducted in the homes of deceased children. All deaths of children under 5 years of age in 10 project areas were investigated. In the other 5 projects, representative cases were selected for investigation because of the size of the areas and the large number of deaths. As soon as a child’s death was known to the project staff, a nurse or social worker made a visit to the household concerned to obtain data regarding housing conditions, members of the family, parents of the deceased child, mother’s reproductive history, prenatal care, delivery, breast feeding, and provision of foods and medical attention to the index child. In addition, a medical interviewer sought clinical and pathological information in the hospitals, health centers, or private physicians’ offices where medical attention had been provided. If information was not available or was unsatisfactory, the medical interviewer again visited the home to obtain the history of illness. Findings 1. Nutritional deficiency, which was frequently associated with low birth weight, was the most serious health problem uncovered in the investigation of child mortality. Fifty-seven percent of the children who died before they reached 5 years of age were found to have had immaturity or nutritional deficiency as either the underlying or an associated cause of death. In several areas, two-thirds of the deceased children had one or both of these conditions. These conditions were found more often in rural areas than in urban areas. 2. This study provided the first analysis of causes of death from nutritional deficiency by age at death and by type of deficiency. The peak of mortality was in infancy, as early as the third and fourth months of life, with patterns differing markedly in the 13 Latin American projects. In 6 projects, mortality was excessive in the first few months of life; in 6 others, high rates extended into the second year; and in rural areas of the El Salvador project, mortality from nutritional deficiency continued to be important during the first 5 years of life. Mortality due to protein malnutrition increased to its peak in children 12 to 17 months of age, while nutritional marasmus caused high rates of death in infants from 2 to 6 months old. 3. Only through the study of multiple causes of death was it possible to measure the magnitude of health problems in infancy and childhood. Analysis of associated as well as underlying causes of death was necessary to uncover important interrelationships such as the synergistic action of infectious diseases and nutritional deficiency. 4. Official mortality statistics failed to reveal the real magnitude of health problems. For the 15 projects combined, 13.2 percent of the neonatal deaths had not been registered; in 1 project, half the neonatal deaths had not been registered; and in 2 others, more than one-fourth had not been registered. 23 ''Only 52.5 percent of the data on the death certificates agreed with the underlying causes of death assigned by the investigators. (The investigators used information from hospital and autopsy records and interviews conducted in the homes of the deceased children to make their diagnoses. ) 5. The role of infectious diseases as underlying causes of death was clarified, with diarrheal disease being found to be the principal cause, and measles the second. The investigation revealed that the death rate from infectious diseases was 23 percent higher than the death certificates indicated. . 6. The investigation measured for the first time the effects of abnormal conditions in the mother before and during childbirth and complications of pregnancy and immaturity on mortality. Analysis of multiple causes of death showed that abnormal maternal conditions and difficult labor were associated with death 6 times as often as reported on death certificates. Other complications of pregnancy and childbirth were 10 times as frequent, and conditions of placenta and cord over 4 times as frequent as reported on death certificates. 7. The investigation found that congenital anomalies of the nervous system caused excessive numbers of deaths in three projects. Spina bifida was associated with excessive frequency of deaths in El Salvador and Monterrey, Mexico. In the project in Sherbrooke, Canada, reports showed an excessive incidence of both anencephalus and spina bifida. 8. Several other diseases showed marked variations in patterns of mortality. Mortality from malignant neoplasms in childhood was found to be greater than revealed by mortality statistics of the respective countries. Sudden infant death syndrome was found more frequently among infants of mothers less than 20 years of age than among those of older mothers. 9. The mortality rate of rural children was much higher than that of urban children; however, the mortality rate in the study populations was probably lower than that of many other rural Latin American populations because the rural study areas were close to urban medical centers. The variation in mortality was greatest for children in the second year of life. The highest rural death rate was more than 50 times the rate in suburban California. 10. Excessive reproductive wastage was revealed through the study of mortality in previous pregnancies of the mothers of the deceased children. In Recife and El Salvador, more than 30 percent of the infants from previous pregnancies had died. In projects with high birth rates, high proportions of the deceased infants were of fifth or higher birth orders (50.7 percent in Recife and 48.6 percent in Monterrey). In the Chile project, death rates were 39.4 per 1,000 live first births, compared to 90.6 per 1,000 live births of fifth or higher birth order. 11. Of the infants who died in the postneonatal period, 52.5 percent had been breast-fed for 1 month or longer, while only 18.4 percent of those dying at 6 to 11 months had been breast-fed for 6 months or longer. These figures indicate that breast feeding in Latin America is not the usual method of feeding babies as was once thought. In breast- 24 ''fed infants, fewer deaths were due to diarrheal disease and nutritional deficiency than in those never breast fed. 12. Infant mortality varied inversely with the proportion of mothers receiving prenatal care in an area. The proportion of mothers of deceased infants receiving prenatal care varied from 16.9 percent to 96.7 percent. 13. The level of education of the mother was a valuable indicator of socioeconomic status. In those areas where mothers had little or no education, the families usually had low income, poor housing, deficient water supply and sanitary facilities, and no prenatal or other medical services. Thus, education of the mother is a useful indicator for health planning. 14. The study showed a negative correlation between postneonatal death rates and the percentages of homes having piped water. The inverse relation was even clearer when death rates were correlated with percentages of homes with piped water inside the house. For the Latin American cities combined, 69.4 percent of the families in which neonatal deaths occurred had piped water, 37.1 percent inside the house. In the 8 other areas, 28.8 percent had that service (15.0 percent inside house). Of the families of infants who died in the postneonatal period, lower percentages were supplied with piped water (60.2 in cities and 21.6 in the 8 other areas). 15. This study clearly established that coordinated, community- centered research is a sound method of uncovering health problems and providing data needed for the establishment of effective programs. The data from this investigation may be useful to the World Health Organization and other international agencies for establishing new research and health programs and policies. Recommendations 1. Nutrition. Top priority should be given to providing mothers with adequate medical care and good nutrition. Prevention of low weight at birth and malnutrition in early childhood is much more effective in lowering mortality rates than the care of immature infants and lengthy treatment of malnourished children. The investigators urged the promotion and attainment of an optimum state of nutrition for pregnant and nursing women and for infants and children. Parents must be advised on the best reproductive patterns in respect to the age of the mother and intervals between pregnancies. Mothers should be encouraged to breast feed for a sufficient length of time, and to supplement the infant diet properly during weaning. 2. Education. Closer working relationships should be established between universities and health agencies. In particular: a. Students in the various health disciplines should become acquainted with the status and problems of health in the community. 25 ''b. Universities that plan and conduct research and practical studies in the community should involve the staffs and facilities of the local health services. c. The findings of this investigation should facilitate the selection of priority areas for study in maternal and child health, and serve as a teaching tool to demonstrate the complexity of the factors determining the state of health of community, family, and individual. Training in maternal and child health should include efforts to reach every member of the health team, including midwives, lay midwives, obstetricians and pediatricians. Concerted efforts to attain high quality in delivery of health services should be the aim of teaching and training. 3. Basic health data and statistics. a. The need to record the outcome of each pregnancy in as much detail as possible. The data should include the condition of the newborn, birth weight, signs of life, and the distribution of all live births by age and parity of mothers. b. The need for physicians, including obstetricians and pediatricians, as well as hospital administrators, midwives, nurses, and others attending births, to know and use the WHO definitions of live birth and fetal death. c. The need for complete recording of clinical information and correct medical certification of causes of death, including statements on both underlying and contributory causes. Such data are essential for the analysis of multiple causes of death. 4. Epidemiologic research. The investigation provided an overview of major health problems, some of which need clarification through in- depth epidemiologic research. Other problems require practical research to demonstrate specific and realistic methods for solving them. One epidemiologic problem disclosed by this research is the gravity and complexity of the combined effects of immaturity and nutritional deficiency. Longitudinal research could clarify the full effect of nutritional deficiencies on pregnant women and on pregnancy outcomes. Such research could study the effects of nutritional deficiency in combination with different ages of mothers, reproductive histories, and social and environmental factors. The investigation data showed that fatal congenital anomalies of the nervous system are unusually frequent in certain geographic areas in the Americas. The possible relationship between anomalies and nutritional deficiencies suggests a new area for investigation in depth. The higher incidence in certain areas also opens the possibility for fruitful comparative studies. Data from this study showed that mortality from malignant neoplasms in childhood was greater than official statistics indicated. Leukemia accounted for half of these deaths. A puzzling finding was the frequency of minor anomalies in the children who died from malignant neoplasms. The etiology and incidence of malignant neoplasms in children needs further investigation. While sudden infant death syndrome (SIDS) was relatively infrequent in the areas studied, there was a large enough sample to make statistical 26 ''analyses of the syndrome. The data indicated that SIDS was most frequent among infants of young mothers. Also apparent from the study was the finding that perinatal causes of mortality—conditions of the mother and placenta and cord—were usually associated with several other causes. The investigators recommended that additional geographic studies, similar to the Inter-American Investigation of Mortality, be conducted on the multiple causes of disease and determinants of health throughout the world. % U. S, GOVERNMENT PRINTING OFFICE : 1977—241-186/1059 27 ''ETT IT eee ee '' '' L b . ; F i b t . * i is pace ts ee diviiaib. iit el i ca aa ist sie ea a s . Socata eat ota ns & hs wh s ''PUBLIC HEALTH LIBRARY wii €029178194 '' RET TE LE ET Te EL TE TT Ey ET aE ET 4 JS. DEPARTMENT OF ; HEALTH, f EDUCATION, nie? WELFARE - i B Pe ic Health Service | a Health Services Administ sda, : Bureau of Community Hi alth Services , Rockville, Maryland 20: 57, ‘ Penalty for Private Use $ TT ''