PERINATAL OUTCOME IN HIV INFECTED PREGNANT WOMEN AT TERTIARY CARE HOSPITAL IN NORTH INDIA: ELEVEN YEARS RETROSPECTIVE STUDY

Mother to child transmission (MTCT) of HIV is a major route of infection in children. Aim of this study was to know perinatal outcome in HIV infected pregnant women. This retrospective study conducted from September 2005 to July 2016, carried at G.S.V.M. Medical College, Kanpur U.P. Hospital records of all HIV infected pregnant women and follow up details of babies were obtained. Out of 80 deliveries;65% delivered vaginally, 11 (13.8%) babies were still born and 14(17.5%) were neonatal deaths. 32.5% were low birth weight (LBW).All neonates received nevirapineprophylaxis. 55.2% preferred breast feeding. Four infants died and 2 babies turned HIV positive. In our study, most common cause of perinatal mortality was prematurity, LBW and birth asphyxia. Overall MTCT rate of HIV was 3.4%. To conclude, transmission of HIV infection can be prevented by counseling, adequate antenatal care, antiretroviral therapy (ART) and simultaneously avoiding mixed feeding.


INTRODUCTION
According to HIV sentinel surveillance 2014-15 by the NACO, overall HIV prevalence is 0.29% among antenatal clinic attendees (NACO,GOI,2006) 1 . Young adults especially women of reproductive age group and children are mainly affected (Ezechi OC et al, 2013) 2 . Mother to child transmission of HIV is a major route of new infection in children (Shah NK, 2006;Kennedy D, 2012) 3,4,5 . More than 95% of HIV infection in children are due to vertical transmission (Shah NK, 2006) 4 .20% transmission occur before 36 weeks gestation, 50% in the days before delivery and 30% intrapartum (Kourtis AP, 2001) 6 . Transmission rate for Breast feeding may be as high as 30-40% (Kourtis AP, 2007) 7 . Though children represent only 6% of the HIV infected population they contribute to one-sixth of HIV deaths (Shah NK, 2006) 3 .
The association between maternal HIV status and pregnancy outcome was studied in Tanzania, and the HIV infected mothers were found to have a 75% higher risk of preterm delivery compared with the HIV negative mothers. The risk of perinatal death in the HIV infected group was found to be 89% higher than that in the non-infected group (Habib N, 2008) 8 .
The early diagnosis of children born to HIV DNA-polymerase chain reaction (PCR) and treating children who are diagnosed HIV positive with anti-retroviral (ARV) drugs within their first 12 weeks of life reduces the mortality by 75% (Shah NK, 2006;Kennedy, 2012) 4,5 . Both maternal and fetal outcome can be improved by increasing awareness and effective implementation of PMTCT programme which includes HIV testing facility to all pregnant women with provision of ARV prophylaxis. This retrospective study was conducted to analyze the incidence of HIV transmission in children born to HIV infected pregnant women and neonatal outcome in past 11 years intertiary care hospital of northern India.

Location and duration of study
This retrospective study conducted from September 2005 to July 2016, carried out at G.S.V.M. Medical College, Kanpur U.P. Total 102 women were found seropositive for HIV infection. The hospital records of all HIV infected pregnant women were collected .Out of 102, 80 women delivered in our hospital, rest were aborted or lost to follow up. Data on demographic profile, mode of delivery and neonatal outcome were obtained and analyzed. For HIV positive women detected for the first time and for those who were not on ART during September 2005 to February 2014; single dose Nevirapine 200 mg were given during labour and 2 mg /kg to the neonate soon after the delivery. If she was already on treatment then ART was continued. From the year October, 2012 to July 2016 for HIV positive women ART (triple drug regimen-Tenofovir 300 mg, Lamivudine 300 mg and Efavirenz 600 mg) was started at 14 weeks of gestation or whenever she was diagnosed. Nevirapine 0.2 ml/kg/day was given to all babies from birth through age 4-6 weeks regardless of infant feeding method. Exclusive breast feeding was advised for all women. Follow up of both mother and babies was done. Dry Blood Spot (DBS) of babies was done at 6 weeks, 6 months, 12 month and 18 months. Confirmation of HIV status was only at 18 months of age. All HIV positive babies were referred to ART center and ART was started according to NACO guidelines.

Statistical Analysis
Data analysis was done using simple measures like mean and percentage.

RESULT
Between September 2005 to July 2016, 34924 women were tested for HIV antibodies, out of which 102 women (0.3%) were found seropositive. Out of 102 seropositive women,6 women had spontaneous abortions, 5 women opted for MTP after counseling at gestational age less than 13 weeks, 4 women were lost to follow up, 4 delivered outside town and there were 3 antenatal mortality. Finally, 80 delivered in hospital, in which majority of women were in age group 21-30 years, multigravida (62.7%) and registered in third trimester (58.8%). Mean age of women was 25.2 years and mean parity was 1.6. Six (7.5%) women were neither on ART nor got Nevirapine prophylaxis. CD4 count of 35% women was less than 350 out of which 13.7% had CD4 count <200.52 babies (65%) were born by vaginal delivery and 28 (35%) by caesarean section ( Table 1).
The mean gestational age at delivery was 37.4 weeks.20 (25%) were preterm. 9 women (11.2%) had early preterm and 11(13.8%) had late preterm births. 60 women (75%) delivered at term. 17 were spontaneous. 3 were induced. Causes for preterm induction were PPROM in 2 patients and IUGR in one woman. 10 (12.5%) babies had very low birth weight. 16 (20%) had low birth weight and rest 54(67.5%) had appropriate weight for gestational age. In total 72 live births. 22 babies (30.6%) required nursery admission. Most common cause was prematurity, low birth weight (LBW) and birth asphyxia. All babies got Nevirapine prophylaxis. 32 out of 58 mothers (55.2%) chose to breast feed (babies who crossed the neonatal period). Among the 32 breastfed infants, 10 infants were breast fed for six months, rest were breastfed for variable periods from 2 months to 5 months and were switched to replacement feed (Table -3).    Total still births were 11 (13.8%) and the most common cause was prematurity and women who reported in advanced labour. Main causes of neonatal death were prematurity, birth asphyxia followed by septicemia. To conclude, most common cause of perinatal mortality was prematurity, LBW and birth asphyxia similar to study done in Tshwane South Africa (2010); where also both stillbirth and neonatal mortality rates were significantly higher for HIV positive mothers, with intrapartum asphyxia, preterm labour and infections were main contributing factors 14 15 . A smaller prospective study in Kenya, comparing perinatal outcome in a seropositive group of mothers with that in a matched seronegative group, found a significant increase in preterm birth in the seropositive group (21% v. 9.1%) and a small increase in perinatal mortality was also found in seropositive group 16 . Ellis et al (2002) also commented in their conclusion that seropositive mother was 'more likely to have a perinatal death' 17 . In Indian studies by GautamS et al 11 and Prameela et al 9 ; still birth were less, 3.1% and 3.9% respectively in comparison to current study. Neonatal deaths (17.5%) were also more in comparison to study by Gautam et al 11 (13.8%).
In our study 20 women (25%) delivered preterm (<37 wks). Most common cause of preterm was PROM (75%). It is possible subclinical chorio-amnionitis may more common in HIV infected mothers and this could cause preterm labour and perinatal hypoxia 18,19 20 . but in our study preterm birth rate was 25% which was more than national average of approximately 21% 21 .
In this study, 32.5% babies had low birth weight, while in study by Prameela et al 9 49.2% babies had birth weight <2.5 kg.
Ezechi et al 2 also found low birth weight was significantly higher in HIV positive women as compared to HIV negative women. While in study by Kennedy et al 5  In our study details of both PCR positive babies is given in table 4. Both delivered vaginally, CD4 count of mother of both positive babies was >350 cell/mm 3 and both women were not on triple drug therapy but Nevirapine prophylaxis was given. Marazzi et al (2010) 25 also showed a transmission rate of 50.6% from mother with CD4 count >350 cells/mm 3 and these women were not on ART. Ugochukwu (2010) 26 et al found lower transmission rate when both mother and baby were on prophylaxis. So probable cause of MTCT in current study may be mixed feeding and both women were not on triple drug therapy.
Therefore, recent guidelines and several studies recommend triple drug regimens to prevent PTCT of HIV 27,28,29 . Single dose Nevirapine may also be associated with increase risk of resistance 30 . According to NACO also, PPCT triple drug therapy should be given to all HIV positive pregnant females irrespective of their CD4 count and exclusive breast feeding should be continued for 6 month along with daily nevirapine.
Although previous studies 31,32,33 found an association between HIV infection in pregnancy and increased rates of low birth weight, prematurity, perinatal deaths, birth asphyxia and neonatal admission. In this current study also, incidence of preterm (25%), LBW (32.5%), perinatal deaths (31.3%) and nursery admission (30.6%) was more.
Limitation of this study was being retrospective as these studies are limited by their reliance on data extraction from previous records. Study is from a single center and study population mostly belonged to lower socio-economic status and may not fully representative of entire population and there were many lost to follow up cases. Finally, there was no control groups to compare outcomes.

CONCLUSIONS
Our study indicates that HIV status of the perinatal women affect the birth outcome in terms of preterm labour, low birth weight and perinatal deaths. Maximum perinatal death occurred in those cases, where women did not take any antenatal visit and presented first time in labour. Most common cause of perinatal mortality was prematurity, LBW and birth asphyxia.
Overall MTCT rate of HIV was 3.4%. To conclude, overall MTCT can be prevented by timely detection, effective counseling, adequate antenatal care, ART irrespective of CD4 count and simultaneously avoiding mixed feeding.