The opioid exposed infant 0-36 months Dr Anna Maria Vella

Introduction Today I will be talking about mothers, substance misusing pregnant mothers. It is a longitudinal study carried out over 5 years. I have carried out my study in Malta. Therefore I must start by contextualising the whole scenario.

Malta: Malta is a small island (316 km²) with about 400,000 residents (Census of Population and Housing. 2011). In the past years many services to cater for different addiction problems have been developed, amongst them services for women who misuse illicit drugs and pregnant substance misusing mothers. The service is run from one centre covering the needs for the whole island. 5 doctors work in this centre and I lead the female service provision. Therefore all Maltese pregnant substance misusing mothers fall under my care.

Background Medical services in the Maltese islands: It is noteworthy to say that in Malta there is only 1 general hospital: Mater Dei Hospital. Although there are some private hospitals where Maltese mothers can give birth, all substance misusing mothers go to Mater Dei Hospital for all their maternal medical needs so as to receive the specialist care needed. These one location scenarios have been of great benefit for data collection and follow up of all patients. Patients have only one centre where to resort to for their addiction problems and 1 hospital where to deliver their children and receive the antenatal care needed.

Methodology The study was undertaken between 2012 to 2016. All children born to opioid using mothers were recruited after the mothers gave consent. Ethical consent was obtained from the Malta Medical School Ethical Board, from the University of Malta Ethical Board and from King’s College Ethical Board. Permission to use data was also obtained from the Sedqa’s (National Agency for Addiction) and the National Obstetric Information System (NOIS) data commissioners The study was carried from the beginning of 2012 and will continue till the end of 2016. All children born to opioid misusing mothers were included in the study and followed for 3 years. All mothers were asked for consent so that they and their children would be part of this study. Ethical consent for this study was obtained from the Malta Medical School Ethical Board, from the University of Malta Ethical Board and from King’s College Ethical Board. Permission to use data was also obtained from the Sedqa’s and the National Obstetric Information System data commissioners.

The Mothers: Cohort of 71 mothers who all were on opioids and who gave birth from January 2012 and April 2016 All were of Maltese nationality except 2: one was from Bulgaria and another from Romania.

Weight of Baby/Cigarettes per day smoked by mother The mean weight of the newborns was 2843.38 ± 443.018gms. This was significantly lower than in the general population. (One-Sample T-test (Control = 3203.9) P-value< 0.001 (Bada et al 2002; Minnes et al. 2011; Minozzi et al. 2008) The difference in birth weight between the opioid using mothers and the general population persisted even when corrected for the degree of their cigarette smoking habit.   Weight of Newborn:

Occipital Frontal Circumference of the Newborn The mean size of the head circumference of the infants born to opioid using mothers was smaller than that of their counterparts born to the general population. The mean size was 32.8947 ±1.60724 cms P-value < 0.001 One-Sample T-test (Control = 34.1)

Apgar scores The Apgar score after 1 minute was 8.63 ±1.256 (P = 0.980). This was similar to that of the general population. The Apgar score after 5 minutes was 8.93 ±0.762 (P=0.039). This was statistically different from the general population.

Hospital Stay Infants of opioid using mothers had a significantly longer hospital stay: 22.91 ± 28.068 days (P< 0.001) General population 3.6days. Breast Feeding Only 11.2 % of the opioid using mothers breastfed their neonates in the first 30 days when compared to 64% of the general population (P<0.001)

Fetal growth effects after opioid exposure in utero, such as lower birth weight, smaller head circumference and lower Apgar scores were demonstrated in this study. Variables influencing fetal growth and gestational age at delivery include smoking, multiple drug use and low socioeconomic status: all factors being prevalent in opioid using mothers in the present and previous studies (Cleary et al. 2011; Fischer and Kopf, 2007; Simpson, 1957). It is relevant to note that in the present study, the opioid exposed newborns weighed less and were smaller than those from the general population irrespective of reported smoking habits. The associated low Apgar may be explained by the direct effect of opioids on the newborn’s brain which affects its respiratory system (Angeles et a l. 2007).

Body weight: Boys Age of child in months Average weight(kgs) Boys Centiles 2 4.69 ± 0.57 20 4 6.64 ± 0.76 40 8 8.34 ± 0.96 25 12 9.77 ± 1.40 18 11.41 ± 1.28 50 24 12.26 ± 1.35 30 13.99 ± 1.39 36 14.97 ± 1.49

Body Weight: Girls Age of child in months Average weight(kgs) Girls Centiles 2 4.78 ± 0.72 50 4 6.29 ± 0.91 8 8.35 ± 1.25 12 9.84 ± 2.02 18 11.26 ± 2.09 24 13.15± 2.86 75 30 15.19 ± 3.68 36 15.71± 3.55

Average OFC(cms) Girls Age of child in months Average OFC(cms) Boys Centiles Average OFC(cms) Girls 2 37.34 ± 1.65 10 38.26 ± 3.42 40 4 41.39 ± 0.89 25 40.37 ± 1.12 20 8 44.29 ± 1.33 43.34 ± 1.29 12 46.06 ± 1.21 15 45.62 ± 1.22 18 47.24 ± 1.15 46.92 ± 1.59 50 24 47.96 ± 0.98 48.04 ± 1.71 30 49.20 ± 0.76 48.25 ± 1.06 36 49.17 ± 1.61 No data

Height Age of child in months Average height(cms) Boys Centiles Girls 2 52.54±2.97 <3 54.35±2.75 10 4 61.44±1.51 Between 3-10 59.60±2.87 8 67.86±1.60 67.38±3.21 12 74.50±1.80 72.02±2.57 18 78.83±2.57 79.19±3.26 25 24 85.50±1.80 86.30±3.76 50 30 90.64±2.78 89.75±4.03 36 93.54±1.60 93.75±5.81

Ruth-Griffiths scales: 8 months Tests of Normality (8 Months) Shapiro-Wilk Test Statistic P Locomotion 0.985 0.629 Personal-Social skills 0.976 0.234 Hearing –Language 0.935 0.002 Eye-Hand Coordination 0.925 0.001 Performance 0.986 0.658

Ruth Griffiths scales: 18months Tests of Normality (18months) Shapiro-Wilk Test Statistic P-value Locomotion 0.877 0.000 Personal-Social skills 0.976 0.408 Hearing –Language 0.950 0.035 Eye-Hand Coordination 0.968 0.196 Performance 0.945 0.021

Ruth Griffiths scales: 30 months Shapiro-Wilk Test Statistic P-value Locomotion 0.905 0.007 Personal-Social skills 0.912 0.011 Hearing –Language 0.979 0.760 Eye-Hand Coordination 0.925 0.025 Performance 0.907 0.008 Practical Reasoning 0.934 0.505

Conclusion Children exposed to opioids in utero reach their neurological milestones later than other children. These children were also exposed to nicotine and other substances. Socio-economic status, living conditions and other confounding factors were present.