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Prematurity in the Maltese Islands

Report prepared for the European Parturition Group

C. Savona-Ventura
Associate Professor and Consultant Obstetrician-Gynaecologist Mater Dei University Hospital, Malta

G.G. Buttigieg
Senior Lecturer and Consultant Obstetrician-Gynaecologist Mater Dei University Hospital, Malta

April 2008 Department of Obstetrics-Gynaecology Malta

The World Health Organization defines a preterm birth as birth before 37 completed weeks of gestation or fewer than 259 days since the first day of the last menstrual period. This definition presents problems in defining the borderline between spontaneous miscarrage and birth in cases of infants born dead. There is wide variation in how these borderline infants are registered. There exist further problems with identifying the true gestational age of some pregnancies in the presence of unknown dates of last menstrual period or irregular menses in individual women. Stillbirths in Malta are defined as deaths occurring to babies prior to the completed expulsion or extraction from its mother of a product of conception after 22 weeks of gestation or weighing 500 grams and over.

In general, preterm birth rates have seen a downward or stable trend in many European countries. During the period 1954-1955, the prematurity rate in the main government-run hospital in Malta was reported to be at 9.5%.1 The rate had decreased to a reported 4.7% in 1983-1986 but increased to 5.8% in 1999-2002, the latter increase being noted mainly in the gestational age of 32-36 weeks.2 The reasons for this apparent increase is multifactorial, but in part strongly reflects the increasing obstetric intervention policies in the management of antenatal problems being practiced in the latter period. It may also reflect effectiveness of ascertainment of cases in the different database systems.

The prematurity rate has in a number of studies throughout Europe been reported to be higher in a number of socially-deprived individuals. Maltese women from the lower socio-economic group were in the 1950s shown to have also a higher risk of premature deliveries. The prematurity rate in the early 1950s in women delivering at the only paying hospital in Malta and presumable belonging to a higher economic strata population was reported to be 4.4%. This contrasts with the reported rate of 9.5% reported in the population attending the free government service and presumably derived from the lower social strata group.1 A deeper analysis of women delivering at the government hospital carried out in 1974 failed to show any definite influence of economic status to maternal
1 2

Cachia EA. Prematurity in Malta. Chest-piece 1956, 1(2), 12-6 Savona-Ventura C. Secular trends in obstetric practice in Malta. Int J Risk Safety Med, 2004, 16(4):211-2

age and duration of gestation; but the three-tier social classification used was biased towards low income groups.3 Various studies in the Maltese population have shown a inter-relationship between a higher prematurity risk and social deprivation [Table 1].

Risk parameter Teenage pregnancies compared to mothers aged 20-29 yrs. maternal age <=17 years maternal age 18-19 years Elderly mothers compared to mothers aged 20-29 yrs maternal age 30-34 years maternal age 35-39 years maternal age >=40 years Marital status of mother out-of-wedlock pregnancy Substance abusers Heroin abusers Domestic abuse Spouse-abused women Multiple birth maternities Twin maternities Higher Order maternities Medical conditions complicating pregnancy Hypertensive disease Pre-existing Diabetes Mellitus Gestational Diabetes Mellitus

Odds Ratio 3.15 1.36

Reference 4

5 1.33 1.67 2.28 6 2.35 7 2.02 8 3.00 9.76 21.74 1.95 4.39 2.26 9 10 11 12 12

Table 1: Identified risk parameters for prematurity in the Maltese population

Camilleri AP, Micallef T. Birth-Weight and Socio-Economic factors. A Pilot Study. St. Lukes Hospital Gazette 1976, 11(1):57-61 4 Savona-Ventura C, Grech ES. Risks in pregnant teenagers. Int J GynaecolObstet, 1990, 32(1):7-13 5 Savona-Ventura C., & Grech E.S. Risk factors in Elderly Patients. In E.S. Grech, & C. Savona-Ventura (Eds.). Proceedings: E.S.S.A.R. V Annual Meeting, Malta, September 1987. Malta: Government Press, 1988, 41-54. 6 Savona-Ventura C. Devotees of Venus: A history of Sexuality in Malta. Malta: DISCERN Institute for research on the signs of the times, 2003 7 Savona-Ventura C. Pregnancy in Maltese drug-abusers: a socio-biological study. Europ J Obstet Gynaeco Reprod Biol, 2004, 115:161-5 8 Savona-Ventura C, Savona-Ventura M, Drengsted-Nielsen S, Johansen KS. Domestic abuse in a central Mediterranean pregnant population. Europ J Obstet Gynecol Reprod Biol, 2001, 98(1):3-8 9 C. Savona-Ventura, K. Zammit, S. Grima, M. Gatt. Twin pregnancy outcomes in the Maltese Islands. Int J Gynaecol Obstet, 2007, 98(3):255-6 10 Savona-Ventura C, Gatt M, Vella K, Grima S. Higher Order Multiple Pregnancy Outcomes in the Maltese Islands: 2000-2004. Malta Medical Journal, 2008, 20(1):19-23 11 Savona-Ventura C, Buttigieg GG, Grima S. Outcomes of hypertensive obstetric patients in the Maltese Islands. Int J Gynaecol Obstet, 2008, 101(2):189-91 12 Savona-Ventura C, Zammit K, Grima S, Ellul A, Gatt M. Diabetes in pregnancy: A clinical audit of cases delivered in the Maltese Islands during 19992004. Int J Risk Safety Med, 2007, 19 (4):229-36

Prematurity remains one of the main causes of neonatal mortality and morbidity even in countries that have well-developed comprehensive maternity and neonatal services. On a worldwide scale, the condition accounts for about 10% of all neonatal deaths. In the Maltese Islands, prematurity has always featured as an important cause of neonatal mortality. During the period 1983-86, a low gestational age was associated with 60.9% of early neonatal deaths [41.7% with a gestational age <32 weeks and 19.2% with gestational age of 33-36 weeks]. This reflected a specific early neonatal mortality rate for premature infants of 10.8 per 100 live birth at a gestation less than 37 weeks. In contrast the specific early neonatal mortality rate for mature infants was 0.3 per 100 live mature births.13 A review of the epidemiology and the short-term complications arising from natural or iatrogenic prematurity in modern practice is necessary to assess the true import of this obstetric complication.

Infants born prematurely who survive the neonatal period are also known to be at greater risk for developing long-term serious health problems such as cerebral palsy, chronic lung disease, gastrointestinal problems, mental retardation, vision or hearing loss. A study assessing the epidemiology of cerebral palsy in Maltese children during 1981-1990 confirmed that the unadjusted OR for prematurity comparing CP cases with controls was statistically significant at 11.78 [95% CI: 4.39; 39.30].14 The impact of other long-term complications for prematurity in the Maltese population has yet to be assessed.


Grech ES, Savona-Ventura C. The Obstetric and Gynaecological services in the Maltese Islands - 1987. Malta, 1988, 51. 14 Sciberras C, Mamo J, Savona-Ventura C, Pace Axiaq R. Risk factors for Cerebral Palsy in Malta. Abstracts: Joint Seminar in Paediatrics and Obstetrics & Gynaecology, November 1996, MCOG, Malta, 1996, 37

Epidemiology of Prematurity: Maltese Islands 1999-2006

The interventionist management policies of modern-day obstetrics being practiced in the Maltese Islands, which possibly promoted the observed increase the prematurity rate, is countered by significant improvements in the management of the premature neonate. The true import of these factors in the presence of a developed obstetric and neonatal service needs to be carefully analysed.

Material & Methods All deliveries in the Maltese Islands during the period 1999-2006 were included in the study. Cases with unknown gestational age at delivery data were excluded from the analysis. The study population thus included a total of 23073 maternities with a total of 23422 infants being born to these mothers. These maternities included a total of 1279 delivered at a documented 36 or less completed weeks of gestation.

The data was obtained in anonymous format from the National Obstetric Information System [NOIS] database managed by the Department of Health Information, Malta. This database includes all maternities registered in the Maltese Islands. The data is completed in accordance to the clinical notes after delivery, prior to discharge from hospital or until 28 days of life. This methodology may in fact give rise to an element of bias since unrecorded clinical events will not be registered and may thus not reflect the true picture; while any adverse outcome occurring after in the neonatal period after discharge from hospital would also not be registered.

Statistical analysis between singleton and higher order maternities was performed using the using a standard statistical package MedCalc. Statistical significance was assumed with a probability value <0.05.

Epidemiology During the period under review the prematurity rate amounted to 5.6% of all maternities with 0.6% of this rate being attributed to severe prematurity delivered at a gestational age of 31 completed weeks or less. Thus 6.2% of total infants born were premature [Table 2].

Gestational Age [completed weeks] <=27 28-31 32-34 35-36 >=37 TOTAL

Number of Maternities 51 85 314 847 21776 23073 0.22 0.37 1.36 3.67 94.38 100

Number of Infants born 56 96 363 941 21966 23422 0.24 0.41 1.55 4.02 93.78 100

Table 2: Infants born and maternities by gestational age

Certain criteria of women are at increased risk of having a premature birth. The mean maternal age of women delivering at term was 27.91 + 5.41 years [n = 21744]; a figure that is overall statistically lower than the mean age of women delivering a premature infant [28.65 + 5.87; n = 1295: p<0.0001]. The maternal age tend [Table 3] suggests that women delivering later during their reproductive life have a greater risk of delivering prematurely [maternal age >=30 years: OR = 1.16]. The teenager woman was also more likely to deliver a preterm infant [maternal age <=17 years: OR = 1.44].

Maternal anthoropomorphic parameters similar appear to have a bearing on the prematurity rate which shorter women predisposing to an apparent increased statistically significant rate. This observation influenced the pre-pregnancy Body Mass Index, even though there did not appear to be any significant increased rate related to pre-pregnancy body weight [Table 3].

PARAMETERS Maternal age [mean + sd] <= 17 years 18-19 years 20-29 years 30-39 years >40 years Anthropomorphic parameters Height Pre-pregnancy weight BMI

Mature births [n=21776 maternities] 27.91 + 5.41 385 1.8 930 4.3 12494 57.5 7423 34.1 512 2.4 158.81 + 6.19 64.63 + 13.57 25.61 + 5.09

Premature births [n=1295 maternities] 28.59 + 6.25 33 2.6 43 3.3 671 51.8 503 38.8 45 3.5 158.11 + 6.16 65.21 + 15.24 26.09 + 5.91


p<0.0001 p=0.0001 p=0.14 p=0.001

Table 3: Maternal characteristics

Previous obstetric history similarly appears to be an important determinant for a premature delivery {Table 4] with a statistically higher prematurity rate being noted in multiparous women [Parity 3+: OR = 1.56]. Similarly women with a higher previous miscarriage rate were more likely to deliver prematurely [Previous miscarrage >=2: OR = 1.79]. Women whose obstetric history includes a previous stillbirth were also more likely to deliver prematurely [Previous stillbirth >=1: OR = 3.17]. Women having premature births were more likely to have a history of infertility as evidence by increased use of artificial reproductive technology [ART use: OR = 4.29].

PARAMETERS Maternal Parity [mean + sd] Para 0 Para 1 Para 2 Para 3+ Previous Miscarrages Miscarrage 0 Miscarrage 1 Miscarrage 2 Miscarrage 3+ Previous stillbirth SB >=1 History of Infertility Use of ART

Mature births [n=21776 maternities] 0.75 + 0.97 10906 50.1 7215 33.1 2525 11.6 1128 5.2 0.24 + 1.97 18309 84.1 2813 12.9 484 2.2 158 0.7 134 162 0.6 0.7

Premature births [n=1295 maternities] 0.80 + 1.05 656 50.7 390 30.1 147 11.4 105 8.1 0.26 + 0.65 1059 81.6 171 13.2 46 3.6 21 1.6 24 39 1.9 3.0



p=0.008 p<0.0001 p<0.0001

Table 4: Maternal previous obstetric history

Antenatal course A number of medical and obstetric complications have been shown to predispose to a statistically greater likelihood of terminating in a premature delivery. Women with a multiple pregnancy are more likely to delivery prematurely [OR = 13.52]; as were women who continued to smoke throughout their pregnancy [OR = 1.46]. Medical or obstetric complication such as hypertensive disease [OR = 2.62], pre-existing diabetes mellitus [OR = 7.50], gestational diabetes [OR = 2.4], 1st-2nd trimester bleeding [OR = 1.83], and 3rd trimester bleeding [OR = 9.22] were also more likely to deliver prematurely [Table 5].

PARAMETERS Multiple pregnancy Twin maternities Higher Order Medical conditions Hypertension Pre-existing DM Gestational DM Obstetric complications Bleeding 1st-2nd trim. Bleeding 3rd trimester [not praevia] Smoking during pregnancy

Mature births [n=21776 maternities] 186 2 1305 52 329 780 199 1242 0.9 0.01 6.0 0.2 1.5 3.6 0.9 5.7

Premature births [n=1295 maternities] 147 11 203 20 47 86 108 107 11.4 0.9 15.7 1.5 3.6 6.6 8.3 8.3


p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001

Table 5: Antenatal problems

Maternal consequences Prematurity appears to have significant obstetric consequences on the mother [Table 6]. These deliveries are overall less likely to be planned [OR = 1.52] by induction of labour or elective Caesarean section when compared to term pregnancies. In spite of this observation, about a third [33.9%] of these deliveries are still iatrogenically-induced ones reflecting obstetric situations that necessitate premature intervention. A greater proportion of these interventions are carried out by abdominal delivery. The preference of delivering the premature infant by the abdominal route in preference to the vaginal route, is also reflected by the higher rate of Caesaean deliveries associated with a premature birth [OR = 2.13]. Conversely, the normal and operative vaginal delivery rates are very

much reduced in premature deliveries. A greater proportion are allowed to deliver in the breech position.


Mature births [n=21776 maternities] [n = 21966 births] 8478 2716 15583 5496 878 9 38.9 12.5 70.9 25.0 4.0 0.04

Premature births [n=1295 maternities] [n = 1456 births] 202 237 641 774 28 13 15.6 18.3 44.0 53.2 1.9 0.9


Planned delivery Induced labour Elective caesarean Type of delivery Normal vaginal Caesarean delivery Operative vaginal Assisted breech



Table 6: Maternal consequences

Infant short-term consequences Prematurity definitely present serious neonatal consequences that can lead to the death of the child or to the development of long-term health complications [Table 7]. The prematurely delivered pregnancy is more likely to be associated with the death of the child. Both the stillbirth rate and the neonatal death rates are markedly elevated in the prematurely delivered pregnancy. The majority [n = 37] of premature stillbirths occurred during the antenatal period and only 10 cases occurred intrapartum. The stillbirth rate was markedly higher in cases delivering before 32 weeks [n = 24: 4.7%] than in cases delivering after 32 weeks [n = 23: 2.4%].

The premature infant at birth was more likely to require resuscitation and life support interventions as evidenced by the higher rate of low Apgar scores at 5 minutes associated with premature deliveries [OR = 36.5]. The neonatal period of the premature infant is fraught with risks of significant serious complications such as respiratory distress syndrome [OR = 9.14], hyperbilirubinaemia [OR = 16.0], and sepsis [OR = 16.0]. The registered complications do not reflect those conditions that arose after the first 28 days of life. A greater proportion of infants were more likely to be of low birth weight [OR = 14.4]. These complications contributed to a significantly higher neonatal mortality rate in

the premature infant [OR = 41.0]. The neonatal death rate was markedly higher in cases delivering before 32 weeks [n = 40: 7.8%] than in cases delivering after 32 weeks [n = 20: 2.1%].

PARAMETERS Birth weight [mean + sd] <1000 gm 1000-2499 gm Infant loss Stillbirth Neonatal death Low Apgar score at 5 min Apgar 0 Apgar 1-6 Neonatal complications RDS Hyperbilirubinaemia Sepsis

Mature births [n = 21966 births] 3303 + 446 gm 6 0.02 646 2.9 30 26 52 133 471 49 27 0.1 0.1 0.2 0.6 2.1 0.2 0.1

Premature births [n = 1456 births] 2421 + 711 gm 65 4.5 545 37.4 47 60 56 60 279 46 23 3.2 4.1 3.9 4.1 19.2 3.2 1.6




p<0.0001 p<0.0001 p<0.0001 p<0.0001

Table 7: Infant short-term consequences


Premature deliveries are associated with a significant level of antenatal and neonatal morbidity that results not only in immediate health problems possibly leading to death, but also in a significant increase in long-term morbidity. Survival rates for preterm infants, particularly those of very low birth weight, have improved steadily with advances in neonatal care coupled with significant antenatal therapeutic interventions. Thus, more and more preterm infants are surviving the neonatal period so that an increasing number of such infants are presenting with chronic adverse sequele. Much of the long-term reports have concentrated on sensorineural outcomes, particularly cerebral palsy but also visual, auditory and intellectual impairments.

The neonatal period of preterm infants is more frequently complicated by respiratory problems due mainly to inadequacy of surfactant production. This early complication requires medical interventions that are generally maintained for a significant period of time. The preterm infant who survives this complication has been reported to be at greater risk of abnormal airway function due to chronic lung disease in later childhood. Physical growth may also be stunted.

The short-term morto-morbidity and the long-term morbidity associated with a preterm births necessitates a determined drive to identify those pregnant women at risk so that proactive intervention management can be instituted. At present, the obstetric mangement of preterm labour is frequently reactive with the obstetrician being faced with either a high risk situation requiring early delivery to save the mother or child from the pregnancy complications, or alternatively is faced with a premature onset of labour or rupture of membranes. The management options in these situations are limited to slowing the progress of labour to enable the administration of corticosteroids to accelerate intrauterine surfactant production. This management is not always initiated in sufficient time to see the desired effect and reduce the morto-morbidity risks to the infant. Many of these infants are born by abdominal operation [caesarean section or hysterotomy] to ensure the least possible birth trauma. This delivery option however increases the morbidity to the mother.


The ideal management of prematurity should take a proactive direction. Some individuals are identified as high risk on the basis of their medical and social history. However, proactive intervention in these individuals is still limited to the application of a cervical cerclage suture at the end of the first trimester. Many patients who deliver prematurely do so spontaneously and do not easily present themselves as high risk. Future research should focus on designing an evidenced-based risk analysis score to enable the timely introduction of preventive therapeutic measures in high risk individuals.